No abstract

Virus-specific CD8+ T cells are known to play an important role in the control of HIV infection. In this study we investigated whether there may be qualitative differences in the CD8+ T cell response in HIV-1- and HIV-2-infected individuals that contribute to the relatively efficient control of the latter infection. A molecular comparison of global TCR heterogeneity showed a more oligoclonal pattern of CD8 cells in HIV-1- than HIV-2-infected patients. This was reflected in restricted and conserved TCR usage by CD8+ T cells recognizing individual HLA-A2- and HLA-B57-restricted viral epitopes in HIV-1, with limited plasticity in their response to amino acid substitutions within these epitopes. The more diverse TCR usage observed for HIV-2-specific CD8+ T cells was associated with an enhanced potential for CD8 expansion and IFN-γ production on cross-recognition of variant epitopes. Our data suggest a mechanism that could account for any possible cross-protection that may be mediated by HIV-2-specific CD8+ T cells against HIV-1 infection. Furthermore, they have implications for HIV vaccine development, demonstrating an association between a polyclonal, virus-specific CD8+ T cell response and an enhanced capacity to tolerate substitutions within T cell epitopes.

Liver-related mortality is an increasing problem in human immunodeficiency virus (HIV)/hepatitis B virus (HBV)-coinfected patients receiving highly active antiretroviral therapy (HAART). In HIV-negative patients, HBV chronicity is associated with a reduction in specific T cell responses that can be partially restored by treatment with lamivudine. We studied 5 HIV/HBV-coinfected patients treated with HAART, either with or without addition of a drug with specific anti-HBV activity. Our data show that reconstitution of some HBV-specific T cell responses can also occur in HIV-positive patients after a reduction in HBV load. This potential to recover T cell responses, which has been thought to be critical for HBV control, provides support for the addition of anti-HBV therapy in the treatment of HIV/HBV-coinfected patients.