Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
1.
Eur J Clin Invest ; 46(2): 170-80, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26681320

ABSTRACT

BACKGROUND: Mucosal-associated invariant T (MAIT) cells play an important role in innate host defence. MAIT cells appear to undergo exhaustion and are functionally weakened in chronic viral infections. However, their role in chronic hepatitis C virus (HCV) infection remains unclear. MATERIALS AND METHODS: We investigated the frequency of CD8(+) CD161(++) TCR Vα7.2(+) MAIT cells in a cross-sectional cohort of chronic HCV-infected patients (n = 25) and healthy controls (n = 25). Peripheral blood mononuclear cells were investigated for circulating MAIT cell frequency, liver-homing (CCR5 and CD103), biomarkers of immune exhaustion (PD-1, TIM-3 and CTLA-4), chronic immune activation (CD38 and HLA-DR), and immunosenescence (CD57) by flow cytometry. RESULTS: The frequency of MAIT cells was significantly decreased, and increased signs of immune exhaustion and chronic immune activation were clearly evident on MAIT cells of HCV-infected patients. Decrease of CCR5 on circulating MAIT cells is suggestive of their peripheral loss in chronic HCV-infected patients. MAIT cells also showed significantly increased levels of HLA-DR, CD38, PD-1, TIM-3 and CTLA-4, besides CD57 in chronic HCV disease. CONCLUSIONS: Immune exhaustion and senescence of CD8(+) CD161(++) TCR Vα7.2(+) MAIT cells could contribute to diminished innate defence attributes likely facilitating viral persistence and HCV disease progression.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Hepatitis C, Chronic/immunology , ADP-ribosyl Cyclase 1/immunology , Adult , Antigens, CD/immunology , Biomarkers , CD57 Antigens/immunology , CD8-Positive T-Lymphocytes/metabolism , CTLA-4 Antigen/immunology , Case-Control Studies , Cohort Studies , Cross-Sectional Studies , Female , Flow Cytometry , HLA-DR Antigens/immunology , Hepatitis A Virus Cellular Receptor 2 , Humans , Immunity, Innate/immunology , Immunosenescence/immunology , Integrin alpha Chains/immunology , Lymphocyte Count , Male , Membrane Proteins/immunology , Middle Aged , NK Cell Lectin-Like Receptor Subfamily B/metabolism , Programmed Cell Death 1 Receptor/immunology , Receptors, Antigen, T-Cell, alpha-beta/metabolism , Receptors, CCR5/immunology , Viral Load , Young Adult
2.
Eur J Clin Invest ; 45(5): 466-74, 2015 May.
Article in English | MEDLINE | ID: mdl-25721991

ABSTRACT

BACKGROUND: Hepatitis C virus (HCV) causes persistent disease in ~85% of infected individuals, where the viral replication appears to be tightly controlled by HCV-specific CD8+ T cells. Accumulation of senescent T cells during infection results in considerable loss of functional HCV-specific immune responses. MATERIALS AND METHODS: We characterized the distinct T-cell phenotypes based on the expression of costimulatory molecules CD28 and CD27, senescence markers PD-1 and CD57, chronic immune activation markers CD38 and HLA-DR, and survival marker CD127 (IL-7R) by flow cytometry following activation of T cells using HCV peptides and phytohemagglutinin. RESULTS: HCV-specific CD4+ and CD8+ T cells from chronic HCV (CHC) patients showed increased expression of PD-1. Furthermore, virus-specific CD4+ T cells of CHC-infected subjects displayed relatively increased expression of HLA-DR and CD38 relative to HCV-specific CD8+ T cells. The CD4+ and CD8+ T cells from HCV-infected individuals showed significant increase of late-differentiated T cells suggestive of immunosenescence. In addition, we found that the plasma viral loads positively correlated with the levels of CD57 and PD-1 expressed on T cells. CONCLUSIONS: Chronic HCV infection results in increased turnover of late-senescent T cells that lack survival potentials, possibly contributing to viral persistence. Our findings challenge the prominence of senescent T-cell phenotypes in clinical hepatitis C infection.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cellular Senescence/immunology , Hepatitis C, Chronic/immunology , Interleukin-7 Receptor alpha Subunit/immunology , ADP-ribosyl Cyclase 1/immunology , Adult , CD28 Antigens/immunology , CD57 Antigens/immunology , Case-Control Studies , Female , Flow Cytometry , HLA-DR Antigens/immunology , Humans , Lymphocyte Activation/immunology , Male , Middle Aged , Programmed Cell Death 1 Receptor/immunology , T-Lymphocytes/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 7/immunology , Young Adult
3.
Apoptosis ; 20(4): 466-80, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25577277

ABSTRACT

Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(®) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.


Subject(s)
Apoptosis Regulatory Proteins/genetics , Apoptosis , Hepacivirus/physiology , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/physiopathology , Leukocytes, Mononuclear/cytology , T-Lymphocytes/cytology , Adult , Apoptosis Regulatory Proteins/metabolism , Female , Hepatitis C, Chronic/metabolism , Hepatitis C, Chronic/virology , Humans , Leukocytes, Mononuclear/metabolism , Male , Reactive Oxygen Species/metabolism , Signal Transduction , T-Lymphocytes/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...