Displaying publications 1 - 20 of 53 in total

Abstract:
Sort:
  1. Fulltext Inhibitory effects of compounds from Phyllanthus amarus on nitric oxide production, lymphocyte proliferation, and cytokine release from phagocytes
    Yuandani, Jantan I, Ilangkovan M, Husain K, Chan KM
    Drug Des Devel Ther, 2016;10:1935-45.
    PMID: 27354767 DOI: 10.2147/DDDT.S105651
    Standardized extract of Phyllanthus amarus has previously been shown to have a strong inhibitory effect on phagocytic activity of human neutrophils. The current study was carried out to evaluate the effects of constituents of the extract of P. amarus on nitric oxide (NO) production as well as lymphocyte proliferation and cytokine release from phagocytes. Three compounds, ethyl 8-hydroxy-8-methyl-tridecanoate, 7β,19α dihydroxy-urs-12-ene, and 1,7,8-trihydroxy-2-naphtaldehyde, together with seven known compounds were isolated from the whole plant of P. amarus. The isolated compounds and reference standards, ie, gallic acid, ellagic acid, corilagin, and geraniin, which were quantitatively analyzed in the extracts, were evaluated for their effects on immune cells. Among the compounds tested, the lignans, especially phyltetralin and phyllanthin, showed strong inhibition on lymphocyte proliferation with half maximal inhibitory concentration (IC50) values of 1.07 μM and 1.82 μM, respectively. Ethyl 8-hydroxy-8-methyl-tridecanoate and 1,7,8-trihydroxy-2-naphtaldehyde exhibited strong inhibition on nitric oxide production with IC50 values of 0.91 μM and 1.07 μM, respectively. Of all the compounds, corilagin was the strongest inhibitor of tumor necrosis factor-α release with an IC50 value of 7.39 μM, whereas geraniin depicted the strongest inhibitory activity on interleukin-1β release with an IC50 value of 16.41 μM. The compounds constituting the extract of P. amarus were able to inhibit the innate immune response of phagocytes at different steps.
    Matched MeSH terms: Lymphocyte Activation
  2. Decrease of CD69 levels on TCR Vα7.2+CD4+ innate-like lymphocytes is associated with impaired cytotoxic functions in chronic hepatitis B virus-infected patients
    Yong YK, Tan HY, Saeidi A, Rosmawati M, Atiya N, Ansari AW, et al.
    Innate Immun, 2017 07;23(5):459-467.
    PMID: 28606013 DOI: 10.1177/1753425917714854
    Hepatitis B virus (HBV) infection is a major cause of chronic liver disease that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses represent the key determinants of HBV clearance or persistence. Here, we investigated the role of the early activation marker, CD69 and effector cytokines, granzyme B (GrB) and IFN-γ in the exhaustion of innate-like TCR Vα7.2+CD4+T cells, in 15 individuals with chronic HBV (CHB) infection where six were HBV DNA+ and nine were HBV DNA-. The percentage of cytokine-producing T cells and MAIT cells were significantly perturbed in HBV patients relative to healthy controls (HCs). The intracellular expression of GrB and IFN-γ was significantly reduced in MAIT cells derived from HBV-infected patients as compared to HCs, and the levels correlated with the percentage and levels [mean fluorescence intensity (MFI)] of CD69 expression. The total expression of CD69 (iMFI) was lower in CHB patients as compared to HCs. The frequency of CD69+ cells correlated with the levels of cytokine expression (MFI), particularly in CHB patients as compared to HCs. In summary, the polyfunctionality of peripheral T cells was significantly reduced among CHB patients, especially in the TCR Vα7.2+CD4+T cells, and the levels of cytokine expression correlated with functional cytokine levels.
    Matched MeSH terms: Lymphocyte Activation
  3. Fulltext Rhaphidophora korthalsii modulates peripheral blood natural killer cell proliferation, cytokine secretion and cytotoxicity
    Yeap SK, Omar AR, Ho WY, Beh BK, Ali AM, Alitheen NB
    BMC Complement Altern Med, 2013;13:145.
    PMID: 23800124 DOI: 10.1186/1472-6882-13-145
    Rhaphidophora korthalsii (Araceae) is a root-climber plant which has been widely used in Chinese traditional medicine for cancer and skin disease treatment. Previous reports have recorded its immunomodulatory effects on mice splenocyte and human peripheral blood. This study investigated the potential immunostimulatory effect of Rhaphidophora korthalsii on human PBMC enriched NK cell.
    Matched MeSH terms: Lymphocyte Activation
  4. The artificial loss of Runx1 reduces the expression of quiescence-associated transcription factors in CD4(+) T lymphocytes
    Wong WF, Kohu K, Nagashima T, Funayama R, Matsumoto M, Movahed E, et al.
    Mol Immunol, 2015 Dec;68(2 Pt A):223-33.
    PMID: 26350416 DOI: 10.1016/j.molimm.2015.08.012
    The Runx1 transcription factor cooperates with or antagonizes other transcription factors and plays essential roles in the differentiation and function of T lymphocytes. Previous works showed that Runx1 is expressed in peripheral CD4(+) T cells which level declines after T cell receptor (TCR) activation, and artificial deletion of Runx1 causes autoimmune lung disease in mice. The present study addresses the mechanisms by which Runx1 contributes to the maintenance of peripheral CD4(+) T cell quiescence. Microarray and quantitative RT-PCR analyses were employed to compare the transcriptome of Runx1 -/- CD4(+) T cells to those of unstimulated and TCR-stimulated Runx1 +/- cells. The results identified genes whose expression was modulated similarly by Runx1 deletion and TCR activation. Among them, genes encoding cytokines, chemokines, and Jak/STAT signaling molecules were substantially induced. In Runx1-deleted T cells, simultaneous increases in Il-17A and Rorγc, a known master gene in TH17 differentiation, were observed. In addition, we observed that the loss of Runx1 reduced the transcription of genes encoding quiescence-associated transcription factors, including Foxp1, Foxo1, and Klf2. Interestingly, we identified consensus Runx1 binding sites at the promoter regions of Foxp1, Foxo1, and Klf2 genes, which can be enriched by chromatin immunoprecipitation assay with an anti-Runx1 antibody. Therefore, we suggest that Runx1 may activate, directly or indirectly, the expression of quiescence-associated molecules and thereby contribute to the maintenance of quiescence in CD4(+) T cells.
    Matched MeSH terms: Lymphocyte Activation
  5. Fulltext Coeliac disease: immunogenicity studies of barley hordein and rye secalin-derived peptides
    Wahab WA, Šuligoj T, Ellis J, Côrtez-Real B, Ciclitira PJ
    Int J Exp Pathol, 2016 Aug;97(4):303-309.
    PMID: 27659035 DOI: 10.1111/iep.12199
    Coeliac disease (CD) is an inflammatory disorder of the small intestine. It includes aberrant adaptive immunity with presentation of CD toxic gluten peptides by HLA-DQ2 or DQ8 molecules to gluten-sensitive T cells. A ω-gliadin/C-hordein peptide (QPFPQPEQPFPW) and a rye-derived secalin peptide (QPFPQPQQPIPQ) were proposed to be toxic in CD, as they yielded positive responses when assessed with peripheral blood T-cell clones derived from individuals with CD. We sought to assess the immunogenicity of the candidate peptides using gluten-sensitive T-cell lines obtained from CD small intestinal biopsies. We also sought to investigate the potential cross-reactivity of wheat gluten-sensitive T-cell lines with peptic-tryptic digested barley hordein (PTH) and rye secalin (PTS). Synthesised candidate peptides were deamidated with tissue transglutaminase (tTG). Gluten-sensitive T-cell lines were generated by culturing small intestinal biopsies from CD patients with peptic-tryptic gluten (PTG), PTH or PTS, along with autologous PBMCs for antigen presentation. The stimulation indices were determined by measuring the relative cellular proliferation via incorporation of (3) H-thymidine. The majority of T-cell lines reacted to the peptides studied. There was also cross-reactivity between wheat gluten-sensitive T-cell lines and the hordein, gliadin and secalin peptides. PTH, PTS, barley hordein and rye secalin-derived CD antigen-sensitive T-cell lines showed positive stimulation with PTG. ω-gliadin/C-hordein peptide and rye-derived peptide are immunogenic to gluten-sensitive T-cell lines and potentially present in wheat, rye and barley. Additional CD toxic peptides may be shared.
    Matched MeSH terms: Lymphocyte Activation/immunology
  6. Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation
    Vellasamy S, Tong CK, Azhar NA, Kodiappan R, Chan SC, Veerakumarasivam A, et al.
    Cytotherapy, 2016 10;18(10):1270-83.
    PMID: 27543068 DOI: 10.1016/j.jcyt.2016.06.017
    BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have been identified as pan-immunosuppressant in various in vitro and in vivo inflammatory models. Although the immunosuppressive activity of MSCs has been explored in various contexts, the precise molecular signaling pathways that govern inhibitory functions remain poorly elucidated.

    METHODS: By using a microarray-based global gene expression profiling system, this study aimed to decipher the underlying molecular pathways that may mediate the immunosuppressive activity of umbilical cord-derived MSCs (UC-MSCs) on activated T cells.

    RESULTS: In the presence of UC-MSCs, the proliferation of activated T cells was suppressed in a dose-depended manner by cell-to-cell contact mode via an active cell-cycle arrest at the G0/G1 phase of the cell cycle. The microarray analysis revealed that particularly, IFNG, CXCL9, IL2, IL2RA and CCND3 genes were down-regulated, whereas IL11, VSIG4, GFA1, TIMP3 and BBC3 genes were up-regulated by UC-MSCs. The dysregulated gene clusters associated with immune-response-related ontologies, namely, lymphocyte proliferation or activation, apoptosis and cell cycle, were further analyzed.

    CONCLUSIONS: Among the nine canonical pathways identified, three pathways (namely T-helper cell differentiation, cyclins and cell cycle regulation, and gap/tight junction signalling pathways) were highly enriched with these dysregulated genes. The pathways represent putative molecular pathways through which UC-MSCs elicit immunosuppressive activity toward activated T cells. This study provides a global snapshot of gene networks and pathways that contribute to the ability of UC-MSCs to suppress activated T cells.

    Matched MeSH terms: Lymphocyte Activation/genetics*
  7. Fulltext Immunogenicity of recombinant BCG-based vaccine expressing the 22 kDa of serine repeat antigen (SE22) of Plasmodium falciparum
    Teo WH, Nurul AA, Norazmi MN
    Trop Biomed, 2012 Jun;29(2):239-53.
    PMID: 22735846 MyJurnal
    The Plasmodium falciparum serine repeat antigen (SERA) is one of the promising blood-stage malarial vaccine candidates. In this study, recombinant Mycobacterium bovis bacille Calmette-Guerin (rBCG) expressing the 22 kDa protein (SE22) from the 47 kDa Nterminal domain of serine repeat antigen (SERA), generated in favour of mycobacterium codon usage, elicited specific immune response in BALB/c mice with a mixed Th1/Th2 profile. Immunized sera containing high levels of specific IgG1 and IgG2a against the epitope (as determined by ELISA) were reactive with fixed P. falciparum merozoites as demonstrated by indirect immunofluorescence assay (IFA). Furthermore, the lymphocyte proliferative response to SE22 antigen from rBCG-immunized mice was higher than that of controls. The expression of intracellular cytokines (IL-2, IL-4 and IFNγ) in CD4+- and CD8+-cells was also enhanced following in-vitro stimulation with SE22. These findings indicate that a rBCG-based vaccine candidate expressing a blood-stage antigen of P. falciparum could enhance both humoral and cellular immune responses, thus paving the way for the rational use of rBCG as a vaccine candidate against malaria.
    Matched MeSH terms: Lymphocyte Activation
  8. Fulltext Immunological profiles of immune restoration disease presenting as mycobacterial lymphadenitis and cryptococcal meningitis
    Tan DB, Yong YK, Tan HY, Kamarulzaman A, Tan LH, Lim A, et al.
    HIV Med, 2008 May;9(5):307-16.
    PMID: 18400078 DOI: 10.1111/j.1468-1293.2008.00565.x
    A proportion of HIV patients beginning antiretroviral therapy (ART) develop immune restoration disease (IRD). Immunological characteristics of IRD were investigated in a cohort of HIV patients beginning therapy in Kuala Lumpur, Malaysia.
    Matched MeSH terms: Lymphocyte Activation/immunology
  9. Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8(+) T cells in HIV/TB co-infection
    Saeidi A, Chong YK, Yong YK, Tan HY, Barathan M, Rajarajeswaran J, et al.
    Cell Immunol, 2015 Sep;297(1):19-32.
    PMID: 26071876 DOI: 10.1016/j.cellimm.2015.05.005
    The role of T-cell immunosenescence and functional CD8(+) T-cell responses in HIV/TB co-infection is unclear. We examined and correlated surrogate markers of HIV disease progression with immune activation, immunosenescence and differentiation using T-cell pools of HIV/TB co-infected, HIV-infected and healthy controls. Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8(+) T cells. Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8(+) T cells, besides diminished expression of CD127 (IL-7Rα) on CD57(+)CD4(+) T cells. Notably, intracellular IFN-γ, perforin and granzyme B levels in HIV-specific CD8(+) T cells of HIV/TB co-infected subjects were diminished. Intracellular CD57 levels in HIV gag p24-specific CD8(+) T cells were significantly increased in HIV/TB co-infection. We suggest that HIV-TB co-infection contributes to senescence associated with chronic immune activation, which could be due to functional insufficiency of CD8(+) T cells.
    Matched MeSH terms: Lymphocyte Activation/immunology
  10. Immunogenicity of a recombinant Mycobacterium bovis bacille Calmette-Guèrin expressing malarial and tuberculosis epitopes
    Rapeah S, Norazmi MN
    Vaccine, 2006 Apr 24;24(17):3646-53.
    PMID: 16494975 DOI: 10.1016/j.vaccine.2006.01.053
    Recombinant Mycobacterium bovis bacille Calmette-Guèrin (rBCG) expressing the malarial epitopes F2R(II)EBA and (NANP)3 as well as two T cell epitopes of the M. tuberculosis ESAT-6 antigen, generated in favour of mycobacterium codon usage elicited specific immune response against these epitopes. Immunised Balb/c mice demonstrated an increase in almost all of the IgG subclasses against both malarial epitopes and enhanced splenocyte proliferative response against the malarial epitopes as well as selected peptides of ESAT-6. Furthermore, flow cytometric analyses showed elevated numbers of CD4+ lymphocytes expressing IFN-gamma and IL-2 against the ESAT-6 peptides, suggesting a specific Th1-mediated response. This study demonstrated that expressing malarial and TB epitopes in a single rBCG construct induced appropriate humoral and cellular immune response against immunogenic epitopes from both organisms.
    Matched MeSH terms: Lymphocyte Activation
  11. The immunosuppressive effects of human bone marrow-derived mesenchymal stem cells target T cell proliferation but not its effector function
    Ramasamy R, Tong CK, Seow HF, Vidyadaran S, Dazzi F
    Cell Immunol, 2008 Feb;251(2):131-6.
    PMID: 18502411 DOI: 10.1016/j.cellimm.2008.04.009
    Mesenchymal stem cells (MSC) are non-haematopoietic stem cells that are capable of differentiating into tissues of mesodermal origin. MSC play an important role in supporting the development of fetal and adult haematopoiesis. More recently, MSC have also been found to exhibit inhibitory effect on T cell responses. However, there is little information on the mechanism of this immunosuppression and our study addresses this issue by targeting T cell functions at various level of immune responses. We have generated MSC from human adult bone marrow (BM) and investigated their immunoregulatory function at different phases of T cell responses. MSC showed the ability to inhibit mitogen (CD3/CD28 microbeads)-activated T cell proliferation in a dose-dependent manner. In order to evaluate the specificity of this immunosuppression, the proliferation of CD4(+) and CD8(+) cells were measured. MSC equally inhibit CD4(+) and CD8(+) subpopulations of T cells in response to PHA stimulation. However, the antiproliferative effect of MSC is not due to the inhibition of T cell activation. The expression of early activation markers of T cells, namely CD25 and CD69 were not significantly altered by MSC at 24, 48 and 72h. Furthermore, the immunosuppressive effect of MSC mainly targets T cell proliferation rather than their effector function since cytotoxicity of T cells is not affected. This work demonstrates that the immunosuppressive effect of MSC is exclusively a consequence of an anti-proliferative activity, which targets T cells of different subpopulations. For this reason, they have the potential to be exploited in the control of unwanted immune responses such as graft versus host disease (GVHD) and autoimmunity.
    Matched MeSH terms: Lymphocyte Activation
  12. The inhibition of human T cell proliferation by the caspase inhibitor z-VAD-FMK is mediated through oxidative stress
    Rajah T, Chow SC
    Toxicol Appl Pharmacol, 2014 Jul 15;278(2):100-6.
    PMID: 24768707 DOI: 10.1016/j.taap.2014.04.014
    The caspase inhibitor benzyloxycarbony (Cbz)-l-Val-Ala-Asp (OMe)-fluoromethylketone (z-VAD-FMK) has recently been shown to inhibit T cell proliferation without blocking caspase-8 and caspase-3 activation in primary T cells. We showed in this study that z-VAD-FMK treatment leads to a decrease in intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) levels in activated T cells. The inhibition of anti-CD3-mediated T cell proliferation induced by z-VAD-FMK was abolished by the presence of low molecular weight thiols such as GSH, N-acetylcysteine (NAC) and l-cysteine, whereas d-cysteine which cannot be metabolised to GSH has no effect. These results suggest that the depletion of intracellular GSH is the underlying cause of z-VAD-FMK-mediated inhibition of T cell activation and proliferation. The presence of exogenous GSH also attenuated the inhibition of anti-CD3-induced CD25 and CD69 expression mediated by z-VAD-FMK. However, none of the low molecular weight thiols were able to restore the caspase-inhibitory properties of z-VAD-FMK in activated T cells where caspase-8 and caspase-3 remain activated and processed into their respective subunits in the presence of the caspase inhibitor. This suggests that the inhibition of T cell proliferation can be uncoupled from the caspase-inhibitory properties of z-VAD-FMK. Taken together, the immunosuppressive effects in primary T cells mediated by z-VAD-FMK are due to oxidative stress via the depletion of GSH.
    Matched MeSH terms: Lymphocyte Activation/drug effects*; Lymphocyte Activation/immunology; Lymphocyte Activation/physiology
  13. Comparison of three forms of antigens in the demonstration of cell-mediated immune response in murine toxoplasmosis
    Rahmah N, Khairul Anuar A
    Biochem Biophys Res Commun, 1992 Dec 15;189(2):640-4.
    PMID: 1472034
    Mice were chronically infected with cysts of ME49 strain of Toxoplasma gondii. At different periods post-infection, their spleens were removed and single cell suspensions were made. Lymphocyte transformation experiments were performed on the lymphocyte suspensions using three different kinds of antigens of ME49 strain of T. gondii, namely soluble, excretory/secretory and cystic forms. The results showed that the pattern of lymphocyte responsiveness was dependent on the kind of antigen employed for induction of the blastogenesis. Using soluble and cystic forms of the antigen, different periods of lymphocyte suppression and lymphocyte proliferation were demonstrated. However, with the use of excretory/secretory antigen, no significant suppression of lymphocyte stimulation was noted throughout the course of infection. Thus excretory/secretory antigen may be the best form of antigen for stimulation of the cell-mediated immune response and hence it appears to be a good candidate for vaccine in toxoplasmosis.
    Matched MeSH terms: Lymphocyte Activation*
  14. Fulltext Protective immune response in BALB/c mice induced by DNA vaccine of the ROP8 gene of Toxoplasma gondii
    Parthasarathy S, Fong MY, Ramaswamy K, Lau YL
    Am J Trop Med Hyg, 2013 May;88(5):883-7.
    PMID: 23509124 DOI: 10.4269/ajtmh.12-0727
    Toxoplasmosis in humans and other animals is caused by the protozoan parasite Toxoplasma gondii. During the process of host cell invasion and parasitophorous vacuole formation by the tachyzoites, the parasite secretes Rhoptry protein 8 (ROP8), an apical secretory organelle. Thus, ROP8 is an important protein for the pathogenesis of T. gondii. The ROP8 DNA was constructed into a pVAX-1 vaccine vector and used for immunizing BALB/c mice. Immunized mice developed immune response characterized by significant antibody responses, antigen-specific proliferation of spleen cells, and production of high levels of IFN-γ (816 ± 26.3 pg/mL). Challenge experiments showed significant levels of increase in the survival period (29 days compared with 9 days in control) in ROP8 DNA vaccinated mice after a lethal challenge with T. gondii. Results presented in this study suggest that ROP8 DNA is a promising and potential vaccine candidate against toxoplasmosis.
    Matched MeSH terms: Lymphocyte Activation/immunology*
  15. Fulltext The modulation of PPARγ1 and PPARγ2 mRNA expression by ciglitazone in CD3/CD28-activated naïve and memory CD4+ T cells
    Norazmi MN, Mohamed R, Nurul AA, Yaacob NS
    Clin. Dev. Immunol., 2012;2012:849195.
    PMID: 22548115 DOI: 10.1155/2012/849195
    Given their roles in immune regulation, the expression of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) 1 and 2 isoforms was investigated in human naïve (CD45RA+) and memory (CD45RO+) CD4+ T cells. Stimulation of both types of cells via the CD3/CD28 pathway resulted in high expression of both PPARγ receptors as measured by real-time PCR. Treatment with the PPARγ agonist, ciglitazone, increased PPARγ1 expression but decreased PPARγ2 expression in stimulated naïve and memory cells. Furthermore, when present, the magnitude of both PPARγ receptors expression was lower in naïve cells, perhaps suggesting a lower regulatory control of these cells. Similar profiles of selected proinflammatory cytokines were expressed by the two cell types following stimulation. The induction of PPARγ1 and suppression of PPARγ2 expressions in naïve and memory CD4+ T cells in the presence of ciglitazone suggest that the PPARγ subtypes may have different roles in the regulation of T-cell function.
    Matched MeSH terms: Lymphocyte Activation/drug effects; Lymphocyte Activation/immunology
  16. Increased level of activated gamma delta lymphocytes correlates with disease severity in HIV infection
    Norazmi MN, Arifin H, Jamaruddin MA
    Immunol Cell Biol, 1995 Jun;73(3):245-8.
    PMID: 7590898
    The lymphocyte subset expressing the gamma delta T cell receptor is increased in several infectious diseases including HIV infection. In this study the expression on gamma delta lymphocytes of the T cell activation markers CD25, HLA-DR and CD38, as well as the two isoforms of CD45, namely CD45RA and CD45RO, was determined in the peripheral blood of 56 HIV-infected intravenous drug users and 34 HIV-seronegative blood donors by two-colour flow cytometry. The percentage of gamma delta lymphocytes expressing HLA-DR and CD38 was higher than those in HIV-seronegative controls (P < 0.001 and P < 0.0001, respectively). Furthermore the HLA-DR+gamma delta+ lymphocytes correlated inversely with CD4+ T lymphocyte absolute count (P < 0.02 for both). The levels of gamma delta lymphocytes expressing CD25, CD45RA and CD45RO were similar to those in HIV-seronegative controls. Activated gamma delta lymphocytes may play a role in the HIV disease process and could provide a useful marker for disease progression.
    Matched MeSH terms: Lymphocyte Activation/immunology*
  17. Chronic mucocutaneous candidiasis with deficient CD2 (E receptor) but normal CD3 mononuclear cells
    Noh LM, Hussein SH, Sukumaran KD, Rose I, Abdullah N
    J Clin Lab Immunol, 1991 Jun;35(2):89-93.
    PMID: 1688166
    A case of chronic mucocutaneous candidiasis in a Malaysian child who subsequently developed disseminated tuberculosis and toxoplasmosis is described. The phenotype of her peripheral blood mononuclear cells showed discordance for her T cell markers. The presence of a subpopulation of CD2-/CD3+ mononuclear cells leading to an immunodeficiency state is consistent with failure of activation of CD2-mediated alternative pathway resulting in immunodeficiency. Such abnormal CD2-/CD3+ subpopulations have been described in lepromatous leprosy and foetal abortuses.
    Matched MeSH terms: Lymphocyte Activation
  18. Phytohaemagglutinin-induced lymphocyte transformation in leprosy
    Nelson DS, Nelson M, Thurston JM, Waters MF, Pearson JM
    Clin Exp Immunol, 1971 Jul;9(1):33-43.
    PMID: 5559093
    Matched MeSH terms: Lymphocyte Activation
  19. Fulltext Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells
    Munisvaradass R, Kumar S, Govindasamy C, Alnumair KS, Mok PL
    Int J Mol Sci, 2017 Sep 08;18(9).
    PMID: 28885562 DOI: 10.3390/ijms18091797
    Breast cancer is a common malignancy among women. The innate and adaptive immune responses failed to be activated owing to immune modulation in the tumour microenvironment. Decades of scientific study links the overexpression of human epidermal growth factor receptor 2 (ERBB2) antigen with aggressive tumours. The Chimeric Antigen Receptor (CAR) coding for specific tumour-associated antigens could initiate intrinsic T-cell signalling, inducing T-cell activation, and cytotoxic activity without the need for major histocompatibility complex recognition. This renders CAR as a potentially universal immunotherapeutic option. Herein, we aimed to establish CAR in CD3+ T-cells, isolated from human peripheral blood mononucleated cells that could subsequently target and induce apoptosis in the ERBB2 overexpressing human breast cancer cell line, SKBR3. Constructed CAR was inserted into a lentiviral plasmid containing a green fluorescent protein tag and produced as lentiviral particles that were used to transduce activated T-cells. Transduced CAR-T cells were then primed with SKBR3 cells to evaluate their functionality. Results showed increased apoptosis in SKBR3 cells co-cultured with CAR-T cells compared to the control (non-transduced T-cells). This study demonstrates that CAR introduction helps overcome the innate limitations of native T-cells leading to cancer cell apoptosis. We recommend future studies should focus on in vivo cytotoxicity of CAR-T cells against ERBB2 expressing tumours.
    Matched MeSH terms: Lymphocyte Activation/genetics; Lymphocyte Activation/immunology
  20. Fulltext A case of chronic myeloid leukaemia in blast transformation with leukemic ascites
    Mohd Ridzuan MS, Yap E, Wan Fariza WJ, Fadilah SA, Salwati S
    Med J Malaysia, 2016 04;71(2):85-7.
    PMID: 27326952 MyJurnal
    Chronic Myeloid Leukaemia (CML) is a disease characterised by a distinctive marker that is the Philadelphia Chromosome and an ability to transform into blast phase, which confers a poor prognosis. The median survival was reported to be between three to six months in correlation to blast phase. Extramedullary involvement with CML to sites such as pleural, meningeal and bones have been reported. We report a case of 41-year-old man who was diagnosed with CML in blast phase and presented with ascites. Ultrasound of abdomen showed coarse echotexture of liver suggestive leukaemic infiltration to the liver. The liver profile was severely deranged and associated with coagulopathy. Flow cytometry analysis of the peritoneal fluid revealed presence of myeloblasts consistent with CML in blast crisis with leukaemic ascites. Bone marrow biopsy also confirmed disease transformation. He received standard induction chemotherapy for acute myeloid leukaemia with dose modifications based on liver enzymes performance. Our case highlights an unusual presentation of CML in blast crisis with leukaemic ascites and the challenges in managing cytotoxic treatments due to the liver infiltration.
    Matched MeSH terms: Lymphocyte Activation*
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links