Methods of using interleukin 2 to enhance HIV-specific immune responses.
Interleukin 2 (IL-2) in combination with highly active antiretroviral therapy (HAART) can significantly increase CD4+ T cell counts but does not improve HIV-specific T cell-mediated immune responses that are associated with the control of viral replication. To characterize the immunomodulatory activity of IL-2 in HIV-infected individuals we studied the virus-specific immune response (VIR) by intracellular cytokine expression (interferon gamma, IFN-gamma) after mimicking HIV rebound in peripheral blood mononuclear cells (PBMCs). We found that the whole virus used as HIV antigen was able to activate HIV-specific T cells in the presence of a low concentration (50 IU/ml) of IL-2. Interestingly, increasing concentrations of IL-2 (400 or 1000 IU/ml) in combination with the same amount of HIV doubled the number of HIV-specific T cells. These cells were functionally intact because all of the IFN-gamma-producing CD8+ T cells contained perforin, a marker for cytotoxic T lymphocytes (CTLs). Induction of HIV-specific immune responses by IL-2 was not detected in the absence of HIV antigen both in vitro and in patients treated with HAART, indicating that IL-2 can amplify HIV-specific T cells in the presence of HIV antigen. Therefore, a combination of IL-2 with either structured treatment interruption, which results in a controlled viral load rebound, or with therapeutic vaccination is expected to improve HIV-specific T cell-mediated immune responses.
Xu
Jianqing
J
Research Institute for Genetic and Human Therapy (RIGHT), Washington, DC 20007, USA.
Whitman
Lucia
L
Lori
Franco
F
Lisziewicz
Julianna
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load
D000276:Adjuvants, Immunologic; D007376:Interleukin-2