Phenotypic and Functional Status of Intrahepatic T Cells in Chronic Hepatitis C

Abstract

Polychromatic flow-cytometric assays were used to analyze paired intrahepatic and peripheral lymphocyte samples from 37 patients with chronic hepatitis C. Compared with peripheral cells, intrahepatic T cells were selectively enriched with CD45RO+ memory T cells but had a lower percentage of CD4+ T cells expressing the differentiation markers CD27 and CD28. The percentage of intrahepatic CD45RO+ and CD28+ T cells correlated with the degree of liver inflammation, which suggests that memory T cells at relatively early stages of differentiation are directly involved in liver inflammation. Despite their memory phenotype, intrahepatic T cells were defective in proliferation capability, produced less interferon- gamma in response to stimulation by T cell receptor, and contained less perforin but expressed higher levels of Fas and Fas ligand, compared with their counterparts in peripheral blood. The distinct characteristics of intrahepatic T cells suggest that they play an important role in the immunopathogenesis of chronic hepatitis C.

Coligation of the Hepatitis C Virus Receptor CD81 with CD28 Primes Naive T Lymphocytes to Acquire Type 2 Effector Function

“…Even during strong cytolytic responses, HCV-specific type 1 T cells in the periphery have intrahepatic counterparts that produce type 2 cytokines (22). Similarly, bulk-stimulated intrahepatic CD4 ϩ and CD8 ϩ T cells from chronic patients produce less IFN-␥ than peripheral blood cells and, in the case of CD8 ϩ cells, lower levels of perforin (21), resembling Tc2 lymphocytes (84,85). These data hint at the presence of an elusive type 2 biasing factor in the HCV-infected liver or associated lymphoid tissues, and we suggest that this might include nonspecific effector T CO cells capable of exerting type 2 pressure on HCV-specific cells.…”

CD161 expression on hepatitis C virus–specific CD8+ T cells suggests a distinct pathway of T cell differentiation

“…Our study indicated reduced levels of granzyme B and perforin in CD161+ T cells. HCV‐specific T cells also show low expression (although maturation can occur upon in vitro culture) 7, 8, 33. It is possible that CD161+ T cells, though they are effector memory cells, may have relatively defective killing independent of HCV status.…”

Amphiregulin promotes the immunosuppressive activity of intrahepatic CD4+ regulatory T cells to impair CD8+ T‐cell immunity against hepatitis B virus infection

“…Intrahepatic and splenic immune cells were prepared according to previous publications with several modifications . Briefly, mice were killed by inhalation of carbon dioxide, following which the abdomen of each animal was immediately opened and the spleen was collected and put in ice‐cold PBS.…”

“…Intrahepatic and splenic immune cells were prepared according to previous publications with several modifications. [15][16][17] Briefly, mice were killed by inhalation of carbon dioxide, following which the abdomen of each animal was immediately opened and the spleen was collected and put in ice-cold PBS. Then 10 ml cold PBS (pH 7Á4) was injected via the right ventricle of the heart to perfuse the liver until this organ became blanched and swollen.…”