γδ T cell activation by chronic HIV infection may contribute to intrahepatic Vδ1 compartmentalization and hepatitis C virus disease progression independent of highly active antiretroviral therapy

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 V delta1 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 gamma delta 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 V delta1(+) 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 V delta1 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 V delta 1T cell circulation to normal levels in chronically HIV-infected persons. We conclude that gamma delta T lymphocytes released from tissue to the bloodstream circulation under the influence of chronic HIV infection may contribute to intrahepatic V delta1 compartmentalization and progression of liver disease, independently of HAART.