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Fulltext Recent advances in HIV diagnostics: Point-of-care CD4 + T-cell count & viral load assays

Balakrishnan P, Saravanan S, Vignesh R, Shankar EM

Indian J Med Res, 2023 Nov 01;158(5&6):447-450.
PMID: 38063301 DOI: 10.4103/ijmr.ijmr_1616_23
Matched MeSH terms: CD4-Positive T-Lymphocytes
Fulltext Hyperthermia by near infrared radiation induced immune cells activation and infiltration in breast tumor

Wan Mohd Zawawi WFA, Hibma MH, Salim MI, Jemon K

Sci Rep, 2021 05 13;11(1):10278.
PMID: 33986437 DOI: 10.1038/s41598-021-89740-0

Breast cancer is the most common cancer that causes death in women. Conventional therapies, including surgery and chemotherapy, have different therapeutic effects and are commonly associated with risks and side effects. Near infrared radiation is a technique with few side effects that is used for local hyperthermia, typically as an adjuvant to other cancer therapies. The understanding of the use of near NIR as a monotherapy, and its effects on the immune cells activation and infiltration, are limited. In this study, we investigate the effects of HT treatment using NIR on tumor regression and on the immune cells and molecules in breast tumors. Results from this study demonstrated that local HT by NIR at 43 °C reduced tumor progression and significantly increased the median survival of tumor-bearing mice. Immunohistochemical analysis revealed a significant reduction in cells proliferation in treated tumor, which was accompanied by an abundance of heat shock protein 70 (Hsp70). Increased numbers of activated dendritic cells were observed in the draining lymph nodes of the mice, along with infiltration of T cells, NK cells and B cells into the tumor. In contrast, tumor-infiltrated regulatory T cells were largely diminished from the tumor. In addition, higher IFN-γ and IL-2 secretion was observed in tumor of treated mice. Overall, results from this present study extends the understanding of using local HT by NIR to stimulate a favourable immune response against breast cancer.

Matched MeSH terms: CD4-Positive T-Lymphocytes/immunology
Coinfection between SARS-CoV-2 and HIV with a low CD4+ T-cells count

Suryana K CS

Med J Malaysia, 2021 05;76(3):446-448.
PMID: 34031352

Coronavirus Disease 2019 (COVID-19) is an acute respiratory infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection that started in Wuhan, China in December 2019 and has spread rapidly worldwide. It's critical to take extra precautions if a person has chronic illnesses (comorbidities), such as human immunodeficiency (HIV) infection. Concerns about people living with HIV (PLHIV) having a higher risk of serious COVID-19 disease may be based on the assumption that PLHIV are more likely to be immunocompromised. On the other hand, limited information is available in such people about the characteristics of co-infection between SARS-CoV-2 and Human Immunodeficiency Virus (HIV) who are at greater risk than the general population. Our findings, is of a 32 year old patient who came to Emergency Unit of Wangaya Hospital, Medical Faculty, Udayana University in Denpasar, Bali with complaint of fever, dry cough, and shortness of breath since prior 3 days and had also the past history prolonged fever, weight loss more than 10% 4 weeks. Diagnosis of COVID-19 was confirmed by nasopharyngeal swab sample was used for RT-PCR assay and PITC to confirm HIV infection. He had prolonged hospitalized and discharge after 18 days.

Matched MeSH terms: CD4-Positive T-Lymphocytes/metabolism*
Fulltext Hypomethylating Agents and Immunotherapy: Therapeutic Synergism in Acute Myeloid Leukemia and Myelodysplastic Syndromes

Wong KK, Hassan R, Yaacob NS

Front Oncol, 2021;11:624742.
PMID: 33718188 DOI: 10.3389/fonc.2021.624742

Decitabine and guadecitabine are hypomethylating agents (HMAs) that exert inhibitory effects against cancer cells. This includes stimulation of anti-tumor immunity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients. Treatment of AML and MDS patients with the HMAs confers upregulation of cancer/testis antigens (CTAs) expression including the highly immunogenic CTA NY-ESO-1. This leads to activation of CD4+ and CD8+ T cells for elimination of cancer cells, and it establishes the feasibility to combine cancer vaccine with HMAs to enhance vaccine immunogenicity. Moreover, decitabine and guadecitabine induce the expression of immune checkpoint molecules in AML cells. In this review, the accumulating knowledge on the immunopotentiating properties of decitabine and guadecitabine in AML and MDS patients are presented and discussed. In summary, combination of decitabine or guadecitabine with NY-ESO-1 vaccine enhances vaccine immunogenicity in AML patients. T cells from AML patients stimulated with dendritic cell (DC)/AML fusion vaccine and guadecitabine display increased capacity to lyse AML cells. Moreover, decitabine enhances NK cell-mediated cytotoxicity or CD123-specific chimeric antigen receptor-engineered T cells antileukemic activities against AML. Furthermore, combination of either HMAs with immune checkpoint blockade (ICB) therapy may circumvent their resistance. Finally, clinical trials of either HMAs combined with cancer vaccines, NK cell infusion or ICB therapy in relapsed/refractory AML and high-risk MDS patients are currently underway, highlighting the promising efficacy of HMAs and immunotherapy synergy against these malignancies.

Matched MeSH terms: CD4-Positive T-Lymphocytes
Ethnicity as predictor of immune reconstitution among Malaysian HIV-positive patients treated with highly active antiretroviral therapy

Mohamad Isa II, Abu Bakar S, Ab Rahman AK

J Med Virol, 2020 08;92(8):1173-1181.
PMID: 31957025 DOI: 10.1002/jmv.25680

The impact of sociodemographic and clinical factors on immune recovery and viral load suppression among HIV-1 positive patients treated with HAART particularly in Malaysia is largely unknown. This cross-sectional study enrolled 170 HIV-1-infected individuals of three major ethnicities who attended three HIV outpatient clinics in Malaysia. Questionnaire was used to obtain sociodemographic data while CD4 count and viral load data were gathered from hospital's record. Multiple factors were assessed for their predictive effects on CD4 count recovery (≥500 cells/mm3 ) and viral load suppression (≤50 copies/mL) using binary logistic regression. Most of the subjects were male (149/87.6%), in the age group 30 to 39 years old (78/45.9%) and got infected via homosexual contact (82/48.2%). Indians were associated with 11 times higher chance for CD4 recovery as compared to Malays at 8 to 12 months of HAART (adjusted OR: 10.948, 95% CI: 1.873, 64.001, P = .008). Viral load suppression was positively influenced by intravenous drug use (IVDU) status (adjusted OR: 35.224, 95% CI: 1.234, 1000.489, P = .037) at 4 to 6 months of HAART. Higher pretreatment CD4 count was a positive predictor for both initial immunological and virological responses while higher pretreatment viral load was a negative predictor for virological suppression only. In conclusion, ethnicity plays a significant role in determining early immune reconstitution in Malaysia, besides pretreatment CD4 count. Further studies are needed to identify possible biological factors underlying this association.

Matched MeSH terms: CD4-Positive T-Lymphocytes
Fulltext Burden of Talaromyces marneffei infection in people living with HIV/AIDS in Asia during ART era: a systematic review and meta-analysis

Qin Y, Huang X, Chen H, Liu X, Li Y, Hou J, et al.

BMC Infect Dis, 2020 Jul 29;20(1):551.
PMID: 32727383 DOI: 10.1186/s12879-020-05260-8

BACKGROUND: Talaromyces marneffei (TM) is a dimorphic fungus mainly prevalent in Southeast Asian countries, which often causes disseminated life-threatening infection. TM infection often occurs in HIV/AIDS patients even in the antiretroviral therapy (ART) era. However, there has as yet, not been a systematic analysis of the prevalence of TM infection in HIV-infected populations in Asia.
METHODS: In this study, we searched Pubmed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang from inception to 21 November 2018 for studies reporting TM infection in people living with HIV/AIDS (PLWHA). Our meta-analysis included studies investigating the prevalence of TM infection in PLWHA. Reviews, duplicate studies, and animal studies were excluded. A random effects model was used to estimate pooled prevalence, and meta-regression analysis was conducted to explore potential factors for heterogeneity.
RESULTS: 159,064 patients with HIV infection in 33 eligible studies were included in our meta-analysis. The pooled prevalence of TM infection in PLWHA was 3.6%. Vietnam had the highest prevalence (6.4%), followed by Thailand (3.9%), China (3.3%), India (3.2%) and Malaysia (2.1%). In China, TM infection was most prevalent in South China (15.0%), while the burden in Southwest China was not very heavy (0.3%). CD4+ T-cell counts below 200 cells/mm3 contributed to the increased risk of TM infection in PLWHA (OR 12.68, 95%CI: 9.58-16.77). However, access to ART did not significantly decrease the risk of TM infection in PLWHA.
CONCLUSIONS: The burden of TM infection in Asia is heavy, and varies from region to region. PLWHA in lower latitude areas are more likely to suffer from TM infection. Optimization of diagnostic tools and universal screening for TM in vulnerable people to ensure early case detection and prompt antifungal treatment should be considered.

Matched MeSH terms: CD4-Positive T-Lymphocytes
Fulltext Negligible effect of chicken cytokine IL-12 integration into recombinant fowlpox viruses expressing avian influenza virus neuraminidase N1 on host cellular immune responses

Majid NN, Omar AR, Mariatulqabtiah AR

J Gen Virol, 2020 07;101(7):772-777.
PMID: 32427095 DOI: 10.1099/jgv.0.001428

In comparison to the extensive characterization of haemagglutinin antibodies of avian influenza virus (AIV), the role of neuraminidase (NA) as an immunogen is less well understood. This study describes the construction and cellular responses of recombinant fowlpox viruses (rFWPV) strain FP9, co-expressing NA N1 gene of AIV A/Chicken/Malaysia/5858/2004, and chicken IL-12 gene. Our data shows that the N1 and IL-12 proteins were successfully expressed from the recombinants with 48 kD and 70 kD molecular weights, respectively. Upon inoculation into specific-pathogen-free (SPF) chickens at 105 p.f.u. ml-1, levels of CD3+/CD4+ and CD3+/CD8+ populations were higher in the wild-type fowlpox virus FP9 strain, compared to those of rFWPV-N1 and rFWPV-N1-IL-12 at weeks 2 and 5 time points. Furthermore, rFWPV-N1-IL-12 showed a suppressive effect on chicken body weight within 4 weeks after inoculation. We suggest that co-expression of N1 with or without IL-12 offers undesirable quality as a potential AIV vaccine candidate.

Matched MeSH terms: CD4-Positive T-Lymphocytes
Diminished Co-inhibitory Molecule 2B4 expression is Associated with Preserved iNKT cell Phenotype in HIV Long-term Non-progressors

Ansari AW, Ahmad F, Shankar EM, Kong YY, Tan HY, Jacobs R, et al.

J Acquir Immune Defic Syndr, 2020 May 07.
PMID: 32398557 DOI: 10.1097/QAI.0000000000002399

BACKGROUND: We have previously shown an association of elevated co-inhibitory molecule 2B4 expression with iNKT cells alterations in HIV disease. Herein we show a comparative analysis of 2B4 expression on iNKT cells of HIV long-term non-progressors (LTNPs) and progressors.
METHODS: Anti-retroviral therapy (ART) naïve HIV-seropositive individuals (progressors, n=16) and long-term non-progressors (LTNPs, n=10) were recruited for this study. We employed multi-color flow cytometry on frozen peripheral blood mononuclear cells (PBMCs) to determine iNKT subset frequencies, the levels of co-inhibitory 2B4 expression, and intracellular IFN-γ production. CD1d tetramer was used to characterize iNKT cells.
RESULTS: We report significantly lower level of 2B4 expression on bulk LTNPs iNKT cells as well as on their CD4 subsets compared to HIV progressors. Furthermore, the iNKT cells from LTNPs produced higher amount of IFN-γ than HIV progressors as detected by intracellular cytokine staining. Interestingly, the frequency of 2B4iNKT cells of progressors but not LTNPs significantly correlates with CD4 T cell count, HIV viral load and IFNγ production by iNKT cells.
CONCLUSION: Our results suggest that in addition to suppressed HIV replication, diminished 2B4 expression and associated co-inhibitory signaling, and substantial production of IFN-γ could contribute to preserved iNKT cell phenotype in LTNPs.

Matched MeSH terms: CD4-Positive T-Lymphocytes
Fulltext Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway

Kared H, Tan SW, Lau MC, Chevrier M, Tan C, How W, et al.

Nat Commun, 2020 02 10;11(1):821.
PMID: 32041953 DOI: 10.1038/s41467-020-14442-6

The diversity of the naïve T cell repertoire drives the replenishment potential and capacity of memory T cells to respond to immune challenges. Attrition of the immune system is associated with an increased prevalence of pathologies in aged individuals, but whether stem cell memory T lymphocytes (TSCM) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that TSCM heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/β-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/β-catenin pathway. Functional assays support recent thymic emigrants as the precursors of CD4 TSCM. Our data thus hint that reversing TSCM defects by metabolic targeting of the Wnt/β-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history.

Matched MeSH terms: CD4-Positive T-Lymphocytes/immunology*
Fulltext BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration

Loveridge CJ, Slater S, Campbell KJ, Nam NA, Knight J, Ahmad I, et al.

Oncogene, 2020 02;39(8):1797-1806.
PMID: 31740786 DOI: 10.1038/s41388-019-1106-x

BRF1 is a rate-limiting factor for RNA Polymerase III-mediated transcription and is elevated in numerous cancers. Here, we report that elevated levels of BRF1 associate with poor prognosis in human prostate cancer. In vitro studies in human prostate cancer cell lines demonstrated that transient overexpression of BRF1 increased cell proliferation whereas the transient downregulation of BRF1 reduced proliferation and mediated cell cycle arrest. Consistent with our clinical observations, BRF1 overexpression in a Pten-deficient mouse (PtenΔ/Δ BRF1Tg) prostate cancer model accelerated prostate carcinogenesis and shortened survival. In PtenΔ/Δ BRF1Tg tumours, immune and inflammatory processes were altered, with reduced tumoral infiltration of neutrophils and CD4 positive T cells, which can be explained by decreased levels of complement factor D (CFD) and C7 components of the complement cascade, an innate immune pathway that influences the adaptive immune response. We tested if the secretome was involved in BRF1-driven tumorigenesis. Unbiased proteomic analysis on BRF1-overexpresing PC3 cells confirmed reduced levels of CFD in the secretome, implicating the complement system in prostate carcinogenesis. We further identify that expression of C7 significantly correlates with expression of CD4 and has the potential to alter clinical outcome in human prostate cancer, where low levels of C7 associate with poorer prognosis.

Matched MeSH terms: CD4-Positive T-Lymphocytes/immunology
Treatment modification after second-line failure among people living with HIV in Asia-Pacific

Jiamsakul A, Azwa I, Zhang F, Yunihastuti E, Ditangco R, Kumarasamy N, et al.

Antivir Ther, 2020;25(7):377-387.
PMID: 33616550 DOI: 10.3851/IMP3384

BACKGROUND: The World Health Organization recommends continuation with the failing second-line regimen if third-line option is not available. We investigated treatment outcomes among people living with HIV in Asia who continued with failing second-line regimens compared with those who had treatment modifications after failure.
METHODS: Treatment modification was defined as a change of two antiretrovirals, a drug class change or treatment interruption (TI), all for >14 days. We assessed factors associated with CD4 changes and undetectable viral load (UVL <1,000 copies/ml) at 1 year after second-line failure using linear and logistic regression, respectively. Survival time was analysed using competing risk regression.
RESULTS: Of the 328 patients who failed second-line ART in our cohorts, 208 (63%) had a subsequent treatment modification. Compared with those who continued the failing regimen, the average CD4 cell increase was higher in patients who had a modification without TI (difference =77.5, 95% CI 35.3, 119.7) while no difference was observed among those with TI (difference =-5.3, 95% CI -67.3, 56.8). Compared with those who continued the failing regimen, the odds of achieving UVL was lower in patients with TI (OR=0.18, 95% CI 0.06, 0.60) and similar among those who had a modification without TI (OR=1.97, 95% CI 0.95, 4.10), with proportions of UVL 60%, 22% and 75%, respectively. Survival time was not affected by treatment modifications.
CONCLUSIONS: CD4 cell improvements were observed in those who had treatment modification without TI compared with those on the failing regimen. When no other options are available, maintaining the same failing ART combination provided better VL control than interrupting treatment.

Matched MeSH terms: CD4-Positive T-Lymphocytes
Chronic non-healing ulcers as presenting sign of acquired immunodeficiency syndrome

Nasiri S, Barat T, Bidari-Zerehpoosh F, Mozafari N

Malays Fam Physician, 2020;15(2):30-33.
PMID: 32843942

Atypical forms of herpes simplex virus (HSV) infections, which indicate severe impairment of cellular immunity can be challenging to diagnose. In this paper, we report the case of an atypical HSV infection presenting as chronic nonhealing wounds, which are the first sign of HIV, in a 50-year-old female patient. The lesions had emerged as two large, chronic, and painful ulcerations on the left buttock and labia major 8 months prior. The skin biopsy revealed multinucleated keratinocytes with ground glass nuclei and intranuclear Cowdry type A viral inclusions. A serologic test for HIV-1 was positive. Her CD4+ T-cell count was 42/mm3. Clinicians should be familiar with the dermatologic manifestations of HIV, as they are occasionally key to correctly suspecting an underlying HIV infection, allowing for early diagnosis and treatment.

Matched MeSH terms: CD4-Positive T-Lymphocytes
Fulltext Reduced CD4+ terminally differentiated effector memory T cells in moderate-severe house dust mites sensitized allergic rhinitis patients

Sani MM, Ashari NSM, Abdullah B, Wong KK, Musa KI, Mohamud R, et al.

Asian Pac J Allergy Immunol, 2019 Sep;37(3):138-146.
PMID: 29981564 DOI: 10.12932/AP-191217-0220

BACKGROUND: Terminally differentiated effector memory (TEMRA) T cells exert potent effector function after activation. The proportions of CD4+ T cell subsets especially memory cells in allergic rhinitis (AR) patients sensitized to house dust mites (HDMs) have not been extensively studied.
OBJECTIVE: This study aimed to compare the mean percentages and absolute counts of CD4+ memory T cell subsets between: (i) non-allergic controls and AR patients; (ii) mild AR patients and moderate-severe AR patients.
METHODS: Sensitization to Dermatophagoides farinae and Dermatophagoides pteronyssinus were determined in 33 non -allergic controls, 28 mild AR and 29 moderate-severe AR patients. Flow cytometry was used to determine the percentage of CD4+ na?ve (TN; CD45RA+CCR7+), central memory (TCM; CD45RA-CCR7+), effector memory (TEM; CD45RA-CCR7-) and TEMRA (CD45RA+CCR7-) T cells from the peripheral blood. The absolute counts of CD4+ T cell subsets were obtained by dual platform method from flow cytometer and hematology analyzer.
RESULTS: There were no significant differences in the mean percentages and absolute counts of CD4+ T cell subsets between non-allergic controls and AR patients sensitized to HDMs. However, there were significant reduction in the mean percentage (p=0.0307) and absolute count (p=0.0309) of CD4+ TEMRA cells in moderate-severe AR patients compared to mild AR patients sensitized to HDMs and 13/24 (54.2%) moderate-severe AR patients sensitized to HDMs had persistent symptoms.
CONCLUSION: Reduction in the mean percentage and absolute count of CD4+CD45RA+CCR7- TEMRA cells were observed in moderate-severe AR patients compared to mild AR patients in our population of AR patients sensitized to HDMs.

Matched MeSH terms: CD4-Positive T-Lymphocytes/immunology*; CD4-Positive T-Lymphocytes/metabolism
Application of Ti3 C2 MXene Quantum Dots for Immunomodulation and Regenerative Medicine

Rafieerad A, Yan W, Sequiera GL, Sareen N, Abu-El-Rub E, Moudgil M, et al.

Adv Healthc Mater, 2019 08;8(16):e1900569.
PMID: 31265217 DOI: 10.1002/adhm.201900569

Inflammation is tightly linked to tissue injury. In regenerative medicine, immune activation plays a key role in rejection of transplanted stem cells and reduces the efficacy of stem cell therapies. Next-generation smart biomaterials are reported to possess multiple biologic properties for tissue repair. Here, the first use of 0D titanium carbide (Ti3 C2 ) MXene quantum dots (MQDs) for immunomodulation is presented with the goal of enhancing material-based tissue repair after injury. MQDs possess intrinsic immunomodulatory properties and selectively reduce activation of human CD4+ IFN-γ+ T-lymphocytes (control 87.1 ± 2.0%, MQDs 68.3 ± 5.4%) while promoting expansion of immunosuppressive CD4+ CD25+ FoxP3+ regulatory T-cells (control 5.5 ± 0.7%, MQDs 8.5 ± 0.8%) in a stimulated lymphocyte population. Furthermore, MQDs are biocompatible with bone marrow-derived mesenchymal stem cells and induced pluripotent stem cell-derived fibroblasts. Finally, Ti3 C2 MQDs are incorporated into a chitosan-based hydrogel to create a 3D platform with enhanced physicochemical properties for stem cell delivery and tissue repair. This composite hydrogel demonstrates increased conductivity while maintaining injectability and thermosensitivity. These findings suggest that this new class of biomaterials may help bridge the translational gap in material and stem cell-based therapies for tissue repair and treatment of inflammatory and degenerative diseases.

Matched MeSH terms: CD4-Positive T-Lymphocytes/drug effects; CD4-Positive T-Lymphocytes/metabolism
Fulltext Peripheral immune response in the African green monkey model following Nipah-Malaysia virus exposure by intermediate-size particle aerosol

Lara A, Cong Y, Jahrling PB, Mednikov M, Postnikova E, Yu S, et al.

PLoS Negl Trop Dis, 2019 06;13(6):e0007454.
PMID: 31166946 DOI: 10.1371/journal.pntd.0007454

The ability to appropriately mimic human disease is critical for using animal models as a tool for understanding virus pathogenesis. In the case of Nipah virus (NiV), infection of humans appears to occur either through inhalation, contact with or consumption of infected material. In two of these circumstances, respiratory or sinusoidal exposure represents a likely route of infection. In this study, intermediate-size aerosol particles (~7 μm) of NiV-Malaysia were used to mimic potential routes of exposure by focusing viral deposition in the upper respiratory tract. Our previous report showed this route of exposure extended the disease course and a single animal survived the infection. Here, analysis of the peripheral immune response found minimal evidence of systemic inflammation and depletion of B cells during acute disease. However, the animal that survived infection developed an early IgM response with rapid development of neutralizing antibodies that likely afforded protection. The increase in NiV-specific antibodies correlated with an expansion of the B cell population in the survivor. Cell-mediated immunity was not clearly apparent in animals that succumbed during the acute phase of disease. However, CD4+ and CD8+ effector memory cells increased in the survivor with correlating increases in cytokines and chemokines associated with cell-mediated immunity. Interestingly, kinetic changes of the CD4+ and CD8bright T cell populations over the course of acute disease were opposite from animals that succumbed to infection. In addition, increases in NK cells and basophils during convalescence of the surviving animal were also evident, with viral antigen found in NK cells. These data suggest that a systemic inflammatory response and "cytokine storm" are not major contributors to NiV-Malaysia pathogenesis in the AGM model using this exposure route. Further, these data demonstrate that regulation of cell-mediated immunity, in addition to rapid production of NiV specific antibodies, may be critical for surviving NiV infection.

Matched MeSH terms: CD4-Positive T-Lymphocytes/immunology
Fulltext Intranasal administration of Lignosus rhinocerotis (Cooke) Ryvarden (Tiger Milk mushroom) extract attenuates airway inflammation in murine model of allergic asthma

Muhamad SA, Muhammad NS, Ismail NDA, Mohamud R, Safuan S, Nurul AA

Exp Ther Med, 2019 May;17(5):3867-3876.
PMID: 30988772 DOI: 10.3892/etm.2019.7416

Asthma is a chronic inflammatory disorder in the airways that involves the activation of cells and mediators. Lignosus rhinocerotis (Cooke) Ryvardan or Tiger Milk mushroom is a medicinal mushroom that is traditionally used to treat inflammatory diseases including asthma. In this study, the protective effects of intranasal administration of L. rhinocerotis extract (LRE) in ovalbumin (OVA)-induced airway inflammation mouse model were investigated. Mice were sensitized by intraperitoneal (i.p) injection on days 0 and 14, followed by a daily challenge with 1% OVA from days 21 to 27. Following OVA challenge, LRE and dexamethasone were administered via intranasal and i.p. injection respectively. On day 28, the level of serum immunoglobulin (Ig)E, differential cell counts and T-helper (Th) 2 cytokines in bronchoalveolar lavage fluid (BALF) fluid, cell subset population in lung-draining lymph nodes (LNs), leukocytes infiltration and mucus production in the lungs of the animals was measured. Results demonstrated that intranasal administration of LRE significantly suppressed the level of inflammatory cell counts in BALF as well as populations of CD4+ T-cells in lung draining LNs. Apart from that, LRE also significantly reduced the level of Th2 cytokines in BALF and IgE in the serum in OVA-induced asthma. Histological analysis also demonstrated the amelioration of leukocytes infiltration and mucus production in the lungs. Overall, these findings demonstrated the attenuation of airway inflammation in the LRE-treated mice therefore suggesting a promising alternative for the management of allergic airway inflammation.

Matched MeSH terms: CD4-Positive T-Lymphocytes
Fulltext Immune Biomarkers for Diagnosis and Treatment Monitoring of Tuberculosis: Current Developments and Future Prospects

Yong YK, Tan HY, Saeidi A, Wong WF, Vignesh R, Velu V, et al.

Front Microbiol, 2019;10:2789.
PMID: 31921004 DOI: 10.3389/fmicb.2019.02789

Tuberculosis (TB) treatment monitoring is paramount to clinical decision-making and the host biomarkers appears to play a significant role. The currently available diagnostic technology for TB detection is inadequate. Although GeneXpert detects total DNA present in the sample regardless live or dead bacilli present in clinical samples, all the commercial tests available thus far have low sensitivity. Humoral responses against Mycobacterium tuberculosis (Mtb) antigens are generally low, which precludes the use of serological tests for TB diagnosis, prognosis, and treatment monitoring. Mtb-specific CD4+ T cells correlate with Mtb antigen/bacilli burden and hence might serve as good biomarkers for monitoring treatment progress. Omics-based techniques are capable of providing a more holistic picture for disease mechanisms and are more accurate in predicting TB disease outcomes. The current review aims to discuss some of the recent advances on TB biomarkers, particularly host biomarkers that have the potential to diagnose and differentiate active TB and LTBI as well as their use in disease prognosis and treatment monitoring.

Matched MeSH terms: CD4-Positive T-Lymphocytes
Fulltext Enrichment of gut-derived Fusobacterium is associated with suboptimal immune recovery in HIV-infected individuals

Lee SC, Chua LL, Yap SH, Khang TF, Leng CY, Raja Azwa RI, et al.

Sci Rep, 2018 09 24;8(1):14277.
PMID: 30250162 DOI: 10.1038/s41598-018-32585-x

We explored the gut microbiota profile among HIV-infected individuals with diverse immune recovery profiles following long-term suppressive ART and investigated the relationship between the altered bacteria with markers of immune dysfunction. The microbiota profile of rectal swabs from 26 HIV-infected individuals and 20 HIV-uninfected controls were examined. Patients were classified as suboptimal responders, sIR (n = 10, CD4 T-cell <350 cells/ul) and optimal responders, oIR (n = 16, CD4 T-cell >500 cells/ul) after a minimum of 2 years on suppressive ART. Canonical correlation analysis(CCA) and multiple regression modelling were used to explore the association between fecal bacterial taxa abundance and immunological profiles in optimal and suboptimal responders. We found Fusobacterium was significantly enriched among the HIV-infected and the sIR group. CCA results showed that Fusobacterium abundance was negatively correlated with CD4 T-cell counts, but positively correlated with CD4 T-cell activation and CD4 Tregs. Multiple linear regression analysis adjusted for age, baseline CD4 T-cell count, antibiotic exposure and MSM status indicated that higher Fusobacterium relative abundance was independently associated with poorer CD4 T-cell recovery following ART. Enrichment of Fusobacterium was associated with reduced immune recovery and persistent immune dysfunction following ART. Modulating the abundance of this bacterial taxa in the gut may be a viable intervention to improve immune reconstitution in our setting.

Matched MeSH terms: CD4-Positive T-Lymphocytes/immunology
Broad neutralization response in a subset of HIV-1 subtype C-infected viraemic non-progressors from southern India

Nandagopal P, Bhattacharya J, Srikrishnan AK, Goyal R, Ravichandran Swathirajan C, Patil S, et al.

J Gen Virol, 2018 Mar;99(3):379-392.
PMID: 29458681 DOI: 10.1099/jgv.0.001016

Broadly neutralizing antibodies (bnAbs) have been considered to be potent therapeutic tools and potential vaccine candidates to enable protection against various clades of human immunodeficiency virus (HIV). The generation of bnAbs has been associated with enhanced exposure to antigen, high viral load and low CD4+ T cell counts, among other factors. However, only limited data are available on the generation of bnAbs in viraemic non-progressors that demonstrate moderate to high viraemia. Further, since HIV-1 subtype C viruses account for more than 50 % of global HIV infections, the identification of bnAbs with novel specificities is crucial to enable the development of potent tools to aid in HIV therapy and prevention. In the present study, we analysed and compared the neutralization potential of responses in 70 plasma samples isolated from ART-naïve HIV-1 subtype C-infected individuals with various disease progression profiles against a panel of 30 pseudoviruses. Among the seven samples that exhibited a neutralization breadth of ≥70 %, four were identified as 'elite neutralizers', and three of these were from viraemic non-progressors while the fourth was from a typical progressor. Analysis of the neutralization specificities revealed that none of the four elite neutralizers were reactive to epitopes in the membrane proximal external region (MPER), CD4-binding site and V1V2 or V3 glycan. However, two of the four elite neutralizers exhibited enhanced sensitivity towards viruses lacking N332 glycan, indicating high neutralization potency. Overall, our findings indicate that the identification of potent neutralization responses with distinct epitope specificities is possible from the as yet unexplored Indian population, which has a high prevalence of HIV-1 subtype C infection.

Matched MeSH terms: CD4-Positive T-Lymphocytes
Fulltext Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161++TCR iVα7.2+ Mucosal-Associated Invariant T Cells in Chronic Hepatitis B Virus Infection

Yong YK, Saeidi A, Tan HY, Rosmawati M, Enström PF, Batran RA, et al.

Front Immunol, 2018;9:472.
PMID: 29616020 DOI: 10.3389/fimmu.2018.00472

Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.

Matched MeSH terms: CD4-Positive T-Lymphocytes

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