Displaying publications 41 - 60 of 392 in total

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  1. Yee PTI, Poh CL
    Int J Med Sci, 2018;15(11):1143-1152.
    PMID: 30123051 DOI: 10.7150/ijms.26450
    Enterovirus 71 (EV-A71) is one of the major pathogens causing hand, foot and mouth disease (HFMD). Some strains can lead to neurological disease and fatality in children. Up to date, there is no FDA-approved vaccine to prevent severe HFMD and mortality. Although the inactivated vaccine has advanced to production in China, lack of long-term protection and the requirement of multiple boosters have necessitated the development of other types of vaccines. Recent studies indicate that cellular and not humoral immunity determines the clinical outcome of EV-A71 infections. High levels of cytokines such as IL-1β, IL-6, IL-10 and IFN-γ tend to correlate with clinical severity in patients with pulmonary edema and encephalitis. The live attenuated vaccine may serve as the preferred choice as it can induce excellent humoral and cellular immunity as well as live-long immunity. Expression of certain HLA alleles such as TNF-α promoter type II (-308 allele), HLA-A33 and HLA-DR17 responses have been linked to severe HFMD. However, the high variability of MHC genes could restrict T cell recognition and be a major obstacle in the design of peptide vaccines. Hence, the development of a T cell universal vaccine (incorporating both CD4+ and CD8+ T cell epitopes) that induces broad, multifunctional and cross-reactive CD8+ T cell responses maybe desirable.
    Matched MeSH terms: T-Lymphocytes/immunology*
  2. Abdul Rohim Tualeka, Juliana Jalaludin
    MyJurnal
    The production of ammonia has been increasing over the past few years. Unfortunately, the production does not follow the safety control of ammonia on workers. Indonesia still adopts chemical standard from other countries. Therefore, it requires an ammonia standard at the highest dose without effect or no observed adverse effect level (NOAEL) in the workplace. This research aims to determine standard at the highest dose of without effect through the expression of CD8 cells as well as analysis of histological alteration CD8 lymphocyte between exposed to ammonia group and control. Methods: The study was a laboratory experimental research with a post-test only control group design. The research used Rattus novergicus species as many as 24. NOAEL was determined by middle dose with a location between the smallest and the largest dose. The doses of ammonia were given through inhalation. The histological alteration of CD8 between ammonia in exposed and the control group were analyzed by using the Kruskal Wallis test. Results: NOAEL was found through CD8 located in group 3 with 0.0154 dose mg/kg body weight. There was a differential expression of CD8 lymphocyte cells in the white mice lung between exposed to ammonia group and control (p=0.042). Conclusion: The expression of CD8 lymphocyte cells in the white mice lung exposed to ammonia differs significantly with the number of the expression of CD8 lymphocyte cells in white mice lung at control group. NOAEL was 0.0154 mg/kg body weight of white mice.
    Matched MeSH terms: Lymphocytes; CD8-Positive T-Lymphocytes
  3. Chan KK, Wong RS, Mohamed SM, Ibrahim TA, Abdullah M, Nadarajah VD
    PMID: 22591286
    Bacillus thuringiensis (Bt) parasporal proteins with selective anticancer activity have recently garnered interest. This study determines the efficacy and mode of cell death of Bt 18 parasporal proteins against 3 leukemic cell lines (CEM-SS, CCRF-SB and CCRF-HSB-2).Cell-based biochemical analysis aimed to determine cell viability and the percentage of apoptotic cell death in treated cell lines; ultrastructural analysis to study apoptotic changes and Western blot to identify the parasporal proteins' binding site were performed. Bt 18 parasporal proteins moderately decreased viability of leukemic cells but not that of normal human T lymphocytes. Further purification of the proteins showed changes in inhibition selectivity. Phosphatidylserine externalization, active caspase-3, cell cycle, and ultrastructural analysis confirmed apoptotic activity and S-phase cell-cycle arrest. Western blot analysis demonstrated glyceraldehyde 3-phosphate dehydrogenase as a binding protein. We suggest that Bt 18 parasporal proteins inhibit leukemic cell viability by cell-cycle arrest and apoptosis and that glyceraldehyde 3-phosphate dehydrogenase binding initiates apoptosis.
    Matched MeSH terms: B-Lymphocytes/drug effects; B-Lymphocytes/pathology; B-Lymphocytes/ultrastructure; T-Lymphocytes/drug effects; T-Lymphocytes/pathology; T-Lymphocytes/ultrastructure
  4. Chear CT, Nallusamy R, Chan KC, Mohd Tap R, Baharin MF, Syed Yahya SNH, et al.
    J Clin Immunol, 2021 08;41(6):1178-1186.
    PMID: 33713249 DOI: 10.1007/s10875-021-01017-3
    X-linked agammaglobulinemia is a rare primary immunodeficiency due to a BTK mutation. The patients are characteristically deficient in peripheral B cells and serum immunoglobulins. While they are susceptible to infections caused by bacteria, enteroviruses, and parasites, fungal infections are uncommon in XLA patients. Here, we report a boy of Malay ethnicity who suffered from recurrent upper respiratory tract infections and severe progressive necrotizing fasciitis caused by Saksenaea erythrospora. Immunological tests showed a B cell deficiency and hypogammaglobulinemia. Whole-exome sequencing identified a dinucleotide deletion (c.1580_1581del) in BTK, confirmed by Sanger sequencing and predicted to be disease causing by in silico functional prediction tools (Varsome and MutationTaster2) but was absent in the gnomAD database. This mutation resulted in a frameshift and premature termination (p.C527fs), which disrupted the protein structure. The mother was heterozygous at the mutation site, confirming her carrier status. Flow cytometric analysis of monocyte BTK expression showed it to be absent in the patient and bimodal in the mother. This study describes a novel BTK mutation in a defined hotspot and an atypical fungal phenotype in XLA. Further studies are required to understand the pathogenesis of fungal infection in XLA.
    Matched MeSH terms: B-Lymphocytes/metabolism
  5. Jumat NR, Chong MY, Seman Z, Jamaluddin R, Wong NK, Abdullah M
    Front Immunol, 2017;8:680.
    PMID: 28649252 DOI: 10.3389/fimmu.2017.00680
    Sexual dimorphism in immune response is widely recognized, but few human studies have observed this distinction. Food with endo-immunomodulatory potential may reveal novel sex-biased in vivo interactions. Immunomodulatory effects of Carica papaya were compared between healthy male and female individuals. Volunteers were given fixed meals supplemented with papaya for 2 days. Changes in blood immune profiles and hormone levels were determined. In females, total natural killer (NK) cell percentages decreased (12.7 ± 4.4 vs 14.6 ± 5.8%, p = 0.018, n = 18) while B cells increased (15.2 ± 5.5 vs 14.5 ± 5.0, p = 0.037, n = 18) after papaya consumption. Increased 17β-estradiol (511.1 ± 579.7 vs 282.7 ± 165.0 pmol/l, p = 0.036, n = 9) observed in females may be crucial to this change. Differentiation markers (CD45RA, CD69, CD25) analyzed on lymphocytes showed naïve (CD45RA(+)) non-CD4(+) lymphocytes were reduced in females (40.7 ± 8.1 vs 46.8 ± 5.4%, p = 0.012, n = 8) but not males. A general suppressive effect of papaya on CD69(+) cells, and higher percentage of CD69(+) populations in females and non-CD4 lymphocytes, may be relevant. CD107a(+) NK cells were significantly increased in males (16.8 ± 7.0 vs 14.7 ± 4.8, p = 0.038, n = 9) but not females. Effect in females may be disrupted by the action of progesterone, which was significantly correlated with this population (R = 0.771, p = 0.025, n = 8) after papaya consumption. In males, total T helper cells were increased (33.4 ± 6.4 vs 32.4 ± 6.1%, p = 0.040, n = 15). Strong significant negative correlation between testosterone and CD25(+)CD4(+) lymphocytes, may play a role in the lower total CD4(+) T cells reported in males. Thus, dissimilar immune profiles were elicited in the sexes after papaya consumption and may have sex hormone influence.
    Matched MeSH terms: B-Lymphocytes; T-Lymphocytes, Helper-Inducer
  6. Nordin N, Yeap SK, Zamberi NR, Abu N, Mohamad NE, Rahman HS, et al.
    PeerJ, 2018;6:e3916.
    PMID: 29312812 DOI: 10.7717/peerj.3916
    The nanoparticle as a cancer drug delivery vehicle is rapidly under investigation due to its promising applicability as a novel drug delivery system for anticancer agents. This study describes the development, characterization and toxicity studies of a nanostructured lipid carrier (NLC) system for citral. Citral was loaded into the NLC using high pressure homogenization methods. The characterizations of NLC-citral were then determined through various methods. Based on Transmission Electron Microscope (TEM) analysis, NLC-Citral showed a spherical shape with an average diameter size of 54.12 ± 0.30 nm and a polydipersity index of 0.224 ± 0.005. The zeta potential of NLC-Citral was -12.73 ± 0.34 mV with an entrapment efficiency of 98.9 ± 0.124%, and drug loading of 9.84 ± 0.041%. Safety profile of the formulation was examined via in vitro and in vivo routes to study its effects toward normal cells. NLC-Citral exhibited no toxic effects towards the proliferation of mice splenocytes. Moreover, no mortality and toxic signs were observed in the treated groups after 28 days of treatment. There were also no significant alterations in serum biochemical analysis for all treatments. Increase in immunomodulatory effects of treated NLC-Citral and Citral groups was verified from the increase in CD4/CD3 and CD8/CD3 T cell population in both NLC-citral and citral treated splenocytes. This study suggests that NLC is a promising drug delivery system for citral as it has the potential in sustaining drug release without inducing any toxicity.
    Matched MeSH terms: T-Lymphocytes; CD8-Positive T-Lymphocytes
  7. Arshad L, Jantan I, Bukhari SN, Haque MA
    Front Pharmacol, 2017;8:22.
    PMID: 28194110 DOI: 10.3389/fphar.2017.00022
    The immune system is complex and pervasive as it functions to prevent or limit infections in the human body. In a healthy organism, the immune system and the redox balance of immune cells maintain homeostasis within the body. The failure to maintain the balance may lead to impaired immune response and either over activity or abnormally low activity of the immune cells resulting in autoimmune or immune deficiency diseases. Compounds containing α,β-unsaturated carbonyl-based moieties are often reactive. The reactivity of these groups is responsible for their diverse pharmacological activities, and the most important and widely studied include the natural compounds curcumin, chalcone, and zerumbone. Numerous studies have revealed the mainly immunosuppressive and anti-inflammatory activities of the aforesaid compounds. This review highlights the specific immunosuppressive effects of these natural α,β-unsaturated carbonyl-based compounds, and their analogs and derivatives on different types of immune cells of the innate (granulocytes, monocytes, macrophages, and dendritic cells) and adaptive (T cells, B cells, and natural killer cells) immune systems. The inhibitory effects of these compounds have been comprehensively studied on neutrophils, monocytes and macrophages but their effects on T cells, B cells, natural killer cells, and dendritic cells have not been well investigated. It is of paramount importance to continue generating experimental data on the mechanisms of action of α,β-unsaturated carbonyl-based compounds on immune cells to provide useful information for ensuing research to discover new immunomodulating agents.
    Matched MeSH terms: B-Lymphocytes; T-Lymphocytes
  8. Ahmad S, Hatmal MM, Lambuk L, Al-Hatamleh MAI, Alshaer W, Mohamud R
    Life Sci, 2021 Dec 01;286:120063.
    PMID: 34673116 DOI: 10.1016/j.lfs.2021.120063
    COVID-19 is a multi-faceted disease ranging from asymptomatic to severely ill condition that primarily affects the lungs and could advance to other organs as well. It's causing factor, SARS-CoV-2 is recognized to develop robust cell-mediated immunity that responsible to either control or exaggerate the infection. As an important cell subset that control immune responses and are significantly dysregulated in COVID-19, Tregs is proposed to be considered for COVID-19 management. Among its hallmark, TNFR2 is recently recognized to play important role in the function and survival of Tregs. This review gathers available TNFR2 agonists to directly target Tregs as a potential approach to overcome immune dysregulation that affect the severity in COVID-19. Furthermore, this review performs a rigid body docking of TNF-TNFR2 interaction and such interaction with TNFR2 agonist to predict the optimal targeting approach.
    Matched MeSH terms: T-Lymphocytes, Regulatory/immunology*
  9. Engku Abd Rahman ENS, Irekeola AA, Shueb RH, Mat Lazim N, Mohamud R, Chen X, et al.
    Cytokine, 2023 Oct;170:156341.
    PMID: 37657236 DOI: 10.1016/j.cyto.2023.156341
    TNFR2 is a surface marker of highly suppressive subset of CD4+ FoxP3+ regulatory T cells (Tregs) in humans and mice. This study examined the TNFR2 expression by Tregs of nasopharyngeal carcinoma (NPC) patients and healthy controls. The proliferation, migration, survival of TNFR2+ Tregs, and association with clinicopathological characteristics were assessed. The expression levels of selected cytokines were also determined. The results demonstrated that in both peripheral blood (PB) (10.45 ± 5.71%) and tumour microenvironment (TME) (54.38 ± 16.15%) of NPC patients, Tregs expressed TNFR2 at noticeably greater levels than conventional T cells (Tconvs) (3.91 ± 2.62%, p  0.05), the proportions of PB and TME TNFR2+ Tregs in NPC patients showed more proliferative, higher migration capacity, and better survival ability, as compared to those in healthy controls. Furthermore, TNFR2+ Tregs from NPC patients expressed significantly higher amounts of IL-6 (p = 0.0077), IL-10 (p = 0.0001), IFN-γ (p = 0.0105) and TNF-α (p 
    Matched MeSH terms: T-Lymphocytes, Regulatory*
  10. Sadeghi A, Tahmasebi S, Mahmood A, Kuznetsova M, Valizadeh H, Taghizadieh A, et al.
    J Cell Physiol, 2021 Apr;236(4):2829-2839.
    PMID: 32926425 DOI: 10.1002/jcp.30047
    In the course of the coronavirus disease 2019 (COVID-19), raising and reducing the function of Th17 and Treg cells, respectively, elicit hyperinflammation and disease progression. The current study aimed to evaluate the responses of Th17 and Treg cells in COVID-19 patients compared with the control group. Forty COVID-19 intensive care unit (ICU) patients were compared with 40 healthy controls. The frequency of cells, gene expression of related factors, as well as the secretion levels of cytokines, were measured by flow cytometry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay techniques, respectively. The findings revealed a significant increase in the number of Th17 cells, the expression levels of related factors (RAR-related orphan receptor gamma [RORγt], IL-17, and IL-23), and the secretion levels of IL-17 and IL-23 cytokines in COVID-19 patients compared with controls. In contrast, patients had a remarkable reduction in the frequency of Treg cells, the expression levels of correlated factors (Forkhead box protein P3 [FoxP3], transforming growth factor-β [TGF-β], and IL-10), and cytokine secretion levels (TGF-β and IL-10). The ratio of Th17/Treg cells, RORγt/FoxP3, and IL-17/IL-10 had a considerable enhancement in patients compared with the controls and also in dead patients compared with the improved cases. The findings showed that enhanced responses of Th17 cells and decreased responses of Treg cells in 2019-n-CoV patients compared with controls had a strong relationship with hyperinflammation, lung damage, and disease pathogenesis. Also, the high ratio of Th17/Treg cells and their associated factors in COVID-19-dead patients compared with improved cases indicates the critical role of inflammation in the mortality of patients.
    Matched MeSH terms: T-Lymphocytes, Regulatory/immunology*
  11. Abdullah M, Chai PS, Chong MY, Tohit ER, Ramasamy R, Pei CP, et al.
    Cell Immunol, 2012;272(2):214-9.
    PMID: 22078320 DOI: 10.1016/j.cellimm.2011.10.009
    Differences in gender immune response have resulted in differences in immune protection and susceptibility to inflammatory diseases. Cultured peripheral blood mononuclear cells (PBMC) are widely used in immunomodulation studies, yet the influence of gender is usually not considered. We examined the effect of in vitro culture and phytohaemagglutinin (PHA) stimulation on PBMC lymphocyte subsets using flowcytometry. Full blood counts of whole blood showed higher levels of lymphocyte in male subjects. Lymphocyte subsets enumeration revealed higher NK cell counts in males and higher B cells in females. Cultured PBMC resulted in significant increases in B and total T cell percentages among females and NK cells among males. PHA stimulated significantly increased percentages of NK and total T cells in males and total activated T cells (CD69+) in females. Our results showed significant gender differences in lymphocyte subsets in cultured conditions. This may affect experimental outcome.
    Matched MeSH terms: B-Lymphocytes/immunology; T-Lymphocytes/immunology
  12. Krishnan K, Ker JE, Mohammed SM, Nadarajah VD
    J Biomed Sci, 2010;17:86.
    PMID: 21073742 DOI: 10.1186/1423-0127-17-86
    Bacillus thuringiensis (Bt), an ubiquitous gram-positive spore-forming bacterium forms parasporal proteins during the stationary phase of its growth. Recent findings of selective human cancer cell-killing activity in non-insecticidal Bt isolates resulted in a new category of Bt parasporal protein called parasporin. However, little is known about the receptor molecules that bind parasporins and the mechanism of anti-cancer activity. A Malaysian Bt isolate, designated Bt18 produces parasporal protein that exhibit preferential cytotoxic activity for human leukaemic T cells (CEM-SS) but is non-cytotoxic to normal T cells or other cancer cell lines such as human cervical cancer (HeLa), human breast cancer (MCF-7) and colon cancer (HT-29) suggesting properties similar to parasporin. In this study we aim to identify the binding protein for Bt18 in human leukaemic T cells.
    Matched MeSH terms: T-Lymphocytes/cytology; T-Lymphocytes/drug effects; T-Lymphocytes/metabolism
  13. Keynan Y, Card CM, Ball BT, Li Y, Plummer FA, Fowke KR
    Clin Microbiol Infect, 2010 Aug;16(8):1179-86.
    PMID: 20670292 DOI: 10.1111/j.1469-0691.2010.03142.x
    Influenza vaccine provides protection against infection with matched strains, and this protection correlates with serum antibody titres. In addition to antibodies, influenza-specific CD8+ T-lymphocyte responses are important in decreasing disease severity and facilitating viral clearance. Because this response is directed at internal, relatively conserved antigens, it affords some cross-protection within a given subtype of influenza virus. With the possibility of a broader A(H1N1) Mexico outbreak in the fall of 2009, it appeared worthwhile studying the degree of cellular immune response-mediated cross-reactivity among influenza virus isolates. The composition of the 2006-2007 influenza vaccine included the A/New Caledonia/20/1999 strain (comprising a virus that has been circulating, and was included in vaccine preparations, for 6-7 years) and two strains not previously included (Wisconsin and Malaysia). This combination afforded us the opportunity to determine the degree of cross-reactive cellular immunity after exposure to new viral strains. We analysed the antibody responses and the phenotype and function of the T cell response to vaccine components. The results obtained show that antibody responses to A/New-Caledonia were already high and vaccination did not increase antibody or cytotoxic T lymphocyte responses. These data suggest that repeated exposure to the same influenza stain results in limited boosting of humoral and cellular immune responses.
    Matched MeSH terms: T-Lymphocytes, Cytotoxic/immunology*; CD8-Positive T-Lymphocytes/immunology*
  14. Sosroseno W, Bird PS, Gemmell E, Seymour GJ
    Oral Microbiol. Immunol., 2006 Dec;21(6):411-4.
    PMID: 17064401
    The aim of this study was to determine the role of CD4 and CD8 cells on specific antibody production by murine Peyer's patch (PP) cells after oral immunization with Actinomyces viscosus in mice. Female DBA/2 mice were orally immunized with three low doses of heat-killed A. viscosus. Sham-immunized mice served as a control group. Mice were depleted of CD4 or CD8 cells by intraperitoneal injection of anti-CD4 or anti-CD8 antibodies daily for 3 days before oral immunization. One week after the last oral immunization, PPs were removed and cell suspensions were cultured with A. viscosus. Specific antibody production in the culture supernatants was assessed by enzyme-linked immunosorbent assay. The results showed that oral immunization with A. viscosus induced a predominant specific immunoglobulin A (IgA) response by PP cells and, to a lesser extent, IgM antibodies. Depletion of CD4 but not CD8 cells suppressed the production of specific antibodies. These results suggest that oral immunization with low doses of A. viscosus may induce the production of specific antibodies by murine PP cells in a CD4-cell-dependent fashion.
    Matched MeSH terms: CD4-Positive T-Lymphocytes/physiology*; CD8-Positive T-Lymphocytes/physiology*
  15. Sivapatham G, Gong NC, Pang T
    Twenty-one patients with rheumatoid arthritis (RA) were investigated for various immunological parameters, both humoral and cellular. IgG concentration was 1673+/-266 mg/dl, IgM 259+/-108 mg/dl and IgA 302 +/-7 mg/dl. Enumeration of T lymphocytes in peripheral blood revealed a value of 66% with a B cell count of 10%. Additionally, IgG levels, in 5 selected patients, appeared to fall to normal levels in the course of treatament with D-penicillamine. The significance of these findings are discussed.
    Matched MeSH terms: Lymphocytes
  16. Rusmawati, I., Asma Hanim, H., Naznin, M., Salman, M.S., Norlelawati, A.T.
    MyJurnal
    Introduction: Dengue is one of the commonest infections in Malaysia and it is a notifi able disease. Even
    though the diagnosis of classical dengue fever and dengue haemorrhagic fever can be recognized clinically, the diagnosis remains a challenge in areas where it could not be differentiated with other febrile illnesses. The aim of this study was to focus on the specifi c and consistent morphological features observed in blood fi lms of dengue infection. Materials and Methods: In all 400 cases of dengue infection serologically diagnosed in the Tengku Ampuan Afzan Hospital (HTAA) during May to October 2007, only a total of 27 cases had blood fi lms examined, and thus were included in this study. These blood fi lms were re-examined by two pathologists from HTAA. The full blood count parameters were also retrieved and studied. Results: We consistently found typical reactive lymphocytes [n= 23 (85%)] and thrombocytopenia [n=21, (77.8%)] in the cases. However, leucopenia was present only in 9 cases (33%). Conclusion: The presence of typical reactive lymphocyte is a consistent fi nding in dengue fever and thus could have a signifi cant role in supporting the diagnosis of dengue infection.
    Matched MeSH terms: Lymphocytes
  17. Shaharudin S, Rahim MFA, Muhamad AS
    Int J Prev Med, 2018;9:90.
    PMID: 30450173 DOI: 10.4103/ijpvm.IJPVM_42_17
    Background: The study investigated the effects of isokinetic versus isotonic training among adolescent state-level weightlifters in terms of total leukocytes, total lymphocytes, and its subsets following 24 sessions of training program and a month following training program cessation.

    Methods: Nineteen adolescent state-level weightlifters were assigned into isokinetic or isotonic groups. All participants were recruited from a pool of weightlifters with standardized training program provided by their coach. Series of immunological tests were carried out before the commencement, immediately upon the completion, and a month after the cessation of the additional training program to evaluate total leukocytes and lymphocytes count.

    Results: The results revealed a significant time and group interaction and main effects of time on mean total leukocytes (P < 0.05). Mean total leukocytes count at posttest decreased in both groups. In isotonic group, it was further decreased following 1 month of training cessation (P < 0.05) but not in the isokinetic group. However, the decrement was not high and the values were in the normal range. No significant time and group interaction was observed in total lymphocytes and its subsets count.

    Conclusions: Eight weeks of isokinetic and isotonic additional training with emphasis on shoulder joint only affect mean total leukocytes count in state-level adolescent weightlifters.

    Matched MeSH terms: Lymphocytes
  18. Mark P., Najihah Hanim A., Eshamsol Kamar O., Suhaila A., Irfan M.
    MyJurnal
    Lymphoma is generally a nodal disease and arises from lymphoid tissues or organs. Extranodal lymphoma accounts for almost a third of malignant lymphomas. Squamous cell carcinoma accounts for 90 % of laryngeal carcinoma, while extranodal Non Hodgkin Lymphoma (NHL) attributes only less than 1% of laryngeal neoplasms. Less than 100 of such cases been reported in literature since 1952. As to our best knowledge, no such case was ever reported in our country. We report a case of a 58-year-old gentleman who presented the typical history of laryngeal malignancy however the pathology turned out to be as NHLof Diffuse Large B-cell subtype.
    Matched MeSH terms: B-Lymphocytes
  19. Khairul Anuar A, Rahmah N, Dighe VC, Zurainee MN, Suresh K, Yano A
    JUMMEC, 1999;4:34-38.
    In vitro lymphocyte proliferative response of peripheral blood leucocytes (PBL) to purified Toxoplasma gondii antigen were evaluated by 3[H] methyl thymidine incorporation in patients acutely and chronically infected with Toxoplama gondii. PBL from three patients with acute sylnptonlatic toxoplaslnosis showed no response to T. gondii antigen during the emergence of anti-Toxoplasma 1gM antibodies and the response returned as the infection became chronic. Lymphocytes of twelve chronically-infected patients responded positively to the antigen. In all patients the lymphocyte proliferative response to the mitogen, Concanavalill A (Con A) was normal. Analysis of Toxoplasma proliferative response of PBL from a patient with acute toxoplasrnosis showed that CD8+ cells were responsible for induction of suppression while the response during the chronic infection was lnediated by CD4+ cells. In human toxoplasmosis there was antigen-specific lymphocyte unresponsiveness during the acute phase of the infection and it appears that the initnunesuppression was mediated by CD8+ cells. KEYWORDS: Toxoplasmosis-lymphocyte blastogenesis-antigen specific-CD4+, CD8+
    Matched MeSH terms: Lymphocytes
  20. Wang C, Zainal NS, Chai SJ, Dickie J, Gan CP, Zulaziz N, et al.
    Front Immunol, 2021;12:763086.
    PMID: 34733290 DOI: 10.3389/fimmu.2021.763086
    HPV-independent head and neck squamous cell carcinoma (HNSCC) is a common cancer globally. The overall response rate to anti-PD1 checkpoint inhibitors (CPIs) in HNSCC is ~16%. One major factor influencing the effectiveness of CPI is the level of tumor infiltrating T cells (TILs). Converting TILlow tumors to TILhigh tumors is thus critical to improve clinical outcome. Here we describe a novel DNA vaccines to facilitate the T-cell infiltration and control tumor growth. We evaluated the expression of target antigens and their respective immunogenicity in HNSCC patients. The efficacy of DNA vaccines targeting two novel antigens were evaluated with or without CPI using a syngeneic model. Most HNSCC patients (43/44) co-expressed MAGED4B and FJX1 and their respective tetramer-specific T cells were in the range of 0.06-0.12%. In a preclinical model, antigen-specific T cells were induced by DNA vaccines and increased T cell infiltration into the tumor, but not MDSC or regulatory T cells. The vaccines inhibited tumor growth and improved the outcome alone and upon combination with anti-PD1 and resulted in tumor clearance in approximately 75% of mice. Pre-existence of MAGED4B and FJX1-reactive T cells in HNSCC patients suggests that these widely expressed antigens are highly immunogenic and could be further expanded by vaccination. The DNA vaccines targeting these antigens induced robust T cell responses and with the anti-PD1 antibody conferring excellent tumor control. This opens up an opportunity for combination immunotherapy that might benefit a wider population of HNSCC patients in an antigen-specific manner.
    Matched MeSH terms: T-Lymphocytes/immunology; Lymphocytes, Tumor-Infiltrating/immunology
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