Impaired activation and costimulation of T CD4+ lymphocytes during chronic Hepatitis C infection

被引:0
作者
Barboza, Luisa
Luisa Martens, Maria
Salmen, Siham
Peterson, Darrell L. [2 ]
Montes, Henry
Berrueta, Lisbeth [1 ]
机构
[1] Univ Los Andes, Fac Med, Inst Inmunol Clin, Merida 5101, Venezuela
[2] Univ Los Andes, CAMIULA, Merida 5101, Venezuela
来源
INVESTIGACION CLINICA | 2008年 / 49卷 / 03期
关键词
Hepatitis C virus; T cell activation; CD28; TGF-beta; CD69; CD40L; CD25;
D O I
暂无
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Hepatitis C chronic infection occurs in 80% of the cases and eventually leads to cirrhosis and hepatocellular carcinoma. A deficient adaptive immune response has been described during chronic infection which contributes to viral persistence. This altered T cell response could be associated to deficient costimulation signals during priming of T cells. We have conducted an in vitro study to explore the activation phenomenon of CD4(+) T cells focusing on costimulation via the CD28 receptor, associated to stimulation with purified Hepatitis C (HCV) core antigen. Our study involved the induction of CD69, CD25 and CD40L activation receptors, along with detection of intracellular cytokines such as IFN-gamma, TGF-beta and IL-10. Analysis was performed in chronically HCV infected patients, intrafamilial members of HCV-infected patients and healthy individuals. HCV core antigen induced CD40L expression in CD4(+) cells from intrafamilial members, in contrast to chronically infected patients and control individuals. Association of CD28 crosslinking increased CD69 and IFN-gamma expression in chronically infected patients, suggesting a detriment in this signaling pathway. Additionally, an increased TGF-beta expression was observed in CD4(+) cells from HCV-infected patients, which was corrected by addition of CD28 crosslinking. Our results may contribute to understand the underlying mechanism of T cell tolerance against HCV during chronic infection, and to provide new targets for the designing of therapeutic strategies to control the infection and to offer protective immunity against the virus.
引用
收藏
页码:353 / 367
页数:15
相关论文
共 46 条
[1]  
Aguilar MS, 2001, ANN TROP MED PARASIT, V95, P187, DOI 10.1080/00034980120042944
[2]  
[Anonymous], 1989, Molecular Cloning
[3]   ELISPOT analysis of hepatitis C virus protein-specific IFN-γ-producing peripheral blood lymphocytes in infected humans with and without cirrhosis [J].
Anthony, DD ;
Post, AB ;
Valdez, H ;
Peterson, DL ;
Murphy, M ;
Heeger, PS .
CLINICAL IMMUNOLOGY, 2001, 99 (02) :232-240
[4]   Parallel expansion of human virus-specific FoxP3- effector memory and de novo-generated FoxP3+ regulatory CD8+ T cells upon antigen recognition in vitro [J].
Billerbeck, Eva ;
Blum, Hubert E. ;
Thimme, Robert .
JOURNAL OF IMMUNOLOGY, 2007, 179 (02) :1039-1048
[5]   Lymphocyte reactivity to hepatitis C virus (HCV) antigens shows evidence for exposure to HCV in HCV-seronegative spouses of HCV-infected patients [J].
Bronowicki, JP ;
Vetter, D ;
Uhl, G ;
Hudziak, H ;
Uhrlacher, A ;
Vetter, JM ;
Doffoel, M .
JOURNAL OF INFECTIOUS DISEASES, 1997, 176 (02) :518-522
[6]  
Brown PMJ, 2001, CLIN BIOCHEM, V34, P167, DOI 10.1016/S0009-9120(01)00210-7
[7]   An immunomodulatory role for CD4+CD25+ regulatory T lymphocytes in hepatitis C virus infection [J].
Cabrera, R ;
Tu, ZK ;
Xu, YL ;
Firpi, RJ ;
Rosen, HR ;
Liu, C ;
Nelson, DR .
HEPATOLOGY, 2004, 40 (05) :1062-1071
[8]   Immunopathology of hepatitis C [J].
Chang, KM ;
Rehermann, B ;
Chisari, FV .
SPRINGER SEMINARS IN IMMUNOPATHOLOGY, 1997, 19 (01) :57-68
[9]   Hepatitis C [J].
Cheney, CP ;
Chopra, S ;
Graham, C .
INFECTIOUS DISEASE CLINICS OF NORTH AMERICA, 2000, 14 (03) :633-+
[10]   Unscrambling hepatitis C virus-host interactions [J].
Chisari, FV .
NATURE, 2005, 436 (7053) :930-932