Features and distribution of CD8 T cells with human leukocyte antigen class I-specific receptor expression in chronic hepatitis C

Abstract

CD8+ T cells represent a sizable component of the liver inflammatory infiltrate in chronic hepatitis C and are thought to contribute to immune-mediated tissue injury. Because chronic stimulation may promote the expression by CD8+ T cells of distinct human leukocyte antigen class I-specific natural killer cell receptors (NKRs) susceptible to both inhibiting effector functions and promoting cell survival, we examined the distribution and characteristics of CD8+ T cells with such receptors in chronic hepatitis C patients. NKR CD8+ T cells were detectable in liver and peripheral blood from hepatitis C virus (HCV)-infected patients but were not major subsets. However, the frequency of NKG2A+ CD8+ in the liver and in a lesser extent in the peripheral blood was positively correlated to histological activity in HCV-infected patients. No such correlation was found with KIR+ T cells in liver in HCV-infected patients and with the both NKR CD8+ T cells in hepatitis B virus (HBV) infected patients. Circulating CD8+ T cells expressing KIRs exhibited phenotypic features of memory T cells with exacerbated expression of the senescence marker CD57 in patients. NKG2A+CD8+ T cells were committed T cells that appeared less differentiated than KIR +CD8+ T cells. In HCV-infected patients, their content in perforin was low and similar to that observed in NKG2A-CD8 + T cells; this scenario was not observed in healthy subjects and HBV-infected patients. Both NKG2A and KIRs could inhibit the response of HCV-specific CD8+ T cells ex vivo. Conclusion: These results support the concept that an accumulation in the liver parenchyma of NKR +CD8+ T cells that have functional alterations could be responsible for liver lesions. They provide novel insights into the complexity of liver-infiltrating CD8+ T cells in chronic hepatitis C and reveal that distinct subsets of antigen-experienced CD8+ T cells are differentially sensitive to the pervasive influence of HCV. Copyright © 2007 by the American Association for the Study of Liver Diseases.