• Banishree Saha, Manish C Choudhary, and Shiv K Sarin.
• aInstitute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India bDepartment of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
• AIDS. 2013 Sep 10;27(14):2191-200.

ObjectiveHepatitis C virus (HCV)/HIV coinfection is associated with rapid progression of hepatic fibrosis and liver disease. T-cell response has been implicated in the pathophysiological outcome of the disease.DesignThis study sought to evaluate the role of memory T-cell exhaustion in enhancing immune dysfunction during coinfection.MethodsSixty-four patients were included in the study; HCV monoinfected (n = 21), HIV monoinfected (n = 23), HCV/HIV coinfected (n = 20), and healthy controls (n = 20). Peripheral blood mononuclear cells (PBMCs) were isolated; immunophenotyped and functional assays were performed.ResultsA significant increase in the naive T cells and central memory T cells and a marked reduction in effector memory T cells (TEM) were observed with coinfection as compared to monoinfection. Inhibitory markers programmed death 1 (PD-1) and T-cell immunoglobulin and mucin domain containing molecule 3 (TIM3) were highly upregulated on TEM in coinfection and functionally, these TEM cells displayed lowered proliferation. Increased expression of PD-1 and TIM3 correlated with decreased levels of CD8+CD107a+ TEM cells in coinfection. Pro-inflammatory cytokines interferon-γ and interleukin-2 (IL-2) secretion by TEM cells were also reduced during chronic viral infection. Secretion of IL-10, a human cytokine synthesis inhibitory factor, was significantly upregulated in CD4 TEM with HCV/HIV coinfection in comparison to HCV monoinfection.ConclusionTEM cells play an important role during viral infection and enhanced expression of inhibitory markers is associated with decreased proliferation and cytotoxicity and increased IL-10 production, which was pronounced in HCV/HIV coinfection. Thus, decreased TEM functionality contributes to diminished host immune responses during HCV/HIV coinfection as compared to HCV or HIV monoinfection.

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