gamma delta T cell activation by chronic HIV infection may contribute to intrahepatic V delta 1 compartmentalization and hepatitis C virus disease progression independent of highly active antiretroviral therapy

HIV and hepatis C virus (HCV) coinfection is frequently associated with rap id progression of HCV-related disease, resulting in a higher risk of cirrho sis. Data suggest that natural T cells expressing the V delta1 T cell recep tor rearrangement are recruited in the liver of chronically HCV-infected pa tients and are increased in the peripheral blood of HIV-infected persons. W e studied gamma delta T cell distribution in the peripheral blood and liver of HCV-infected and HIV/HCV-coinfected patients in the presence and absenc e 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 inflammatio n when compared with patients with other liver diseases. Finally, highly ac tive antiretroviral therapy (HAART) was unable to restore V delta 1T cell c irculation to normal levels in chronically HIV-infected persons. We conclud e that gamma delta T lymphocytes released from tissue to the bloodstream ci rculation under the influence of chronic HIV infection may contribute to in trahepatic V delta1 compartmentalization and progression of liver disease, independently of HAART.