γδ T Cell Activation by Chronic HIV Infection May Contribute to Intrahepatic V δ 1 Compartmentalization and Hepatitis C Virus Disease Progression Independent of Highly Active Antiretroviral Therapy

Abstract

HIV and hepatis C virus (HCV) coinfection is frequently associated with rapid progression of HCV-related disease, resulting in a higher risk of cirrhosis. Data suggest that natural T cells expressing the Vδ1 T cell receptor rearrangement are recruited in the liver of chronically HCV-infected patients and are increased in the peripheral blood of HIV-infected persons. We studied γδ T cell distribution in the peripheral blood and liver of HCV-infected and HIV/HCV-coinfected patients in the presence and absence of antiretroviral therapy. We observed that Vδ1⁺ T cells releasing helper T cell type 1 cytokines are compartmentalized not only in the liver of HCV⁺ patients, but also of HIV/HCV-coinfected persons. HIV/HCV patients showed an increased frequency of both peripheral and intrahepatic Vδ1 natural T lymphocytes, resulting in a higher degree of hepatic inflammation when compared with patients with other liver diseases. Finally, highly active antiretroviral therapy (HAART) was unable to restore Vδ1T cell circulation to normal levels in chronically HIV-infected persons. We conclude that γδ T lymphocytes released from tissue to the bloodstream circulation under the influence of chronic HIV infection may contribute to intrahepatic Vδ1 compartmentalization and progression of liver disease, independently of HAART.