Abstract

BARBOZA, Luisa et al. Impaired activation and costimulation of T CD4⁺ lymphocytes during chronic Hepatitis C infection. Invest. clín [online]. 2008, vol.49, n.3, pp.353-367. ISSN 0535-5133.

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-γ, TGF-ß 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-γ expression in chronically infected patients, suggesting a detriment in this signaling pathway. Additionally, an increased TGF-ß 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.

Keywords : Hepatitis C virus; T cell activation; CD28; TGF-ß; CD69; CD40L; CD25.

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