Expression of Regeneration and Tolerance Factor Correlates Directly with Human Immunodeficiency Virus Infection and Inversely with Hepatitis C Virus Infection

Abstract

ABSTRACT Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) cause two of the most prevalent debilitating viral infections. HIV appears to induce a skewing toward a Th2 response, while in HCV infection a Th1 response appears to dominate. Regeneration and tolerance factor (RTF) may participate in driving or sustaining a Th2 cytokine response. The expression of RTF on CD3 + T cells of HIV-seropositive (HIV + ) individuals is increased. The purpose of this study was to compare the expression of RTF during HIV infections with that during HCV infections. Three-color flow-cytometric analysis of peripheral blood collected from HIV + HCV-seropositive (HCV + ), HIV- and HCV-seropositive (HIV + HCV + ), and HIV- and HCV-seronegative (HIV − HCV − ) individuals was performed. Levels of RTF expression on T-lymphocyte subsets from these groups were compared, as were levels of RTF expression on activated T cells expressing CD38 and HLA-DR, to determine the relationship of RTF expression to these infections. We demonstrated that the expression of RTF on surfaces of T cells from HIV + individuals is upregulated and that its expression on T cells from HCV + individuals is downregulated. A twofold increase in the mean channel fluorescence of RTF on CD3 + T cells was seen in both HIV + and HIV + HCV + individuals compared to HIV − HCV − individuals. HCV + individuals had lower levels of RTF expression than HIV − HCV − individuals ( P < 0.005 for CD4 + ; P < 0.0005 for CD8 + ). In terms of percentages of T cells expressing RTF, the groups were ranked as follows: HIV + > HIV + HCV + > HIV − HCV − > HCV + . The results indicate that RTF expression correlates with HIV-associated immune activation and may be associated with Th2-type responses.