Interleukin‐12 is necessary for the priming of CD4+ T cells required during the elicitation of HIV‐1 gp120‐specific cytotoxic T‐lymphocyte function

Abstract

The mechanism of the T-cell response and cytokine induction to restrict human immunodeficiency virus 1 (HIV-1) infection is not clear. During early infection, HIV-infected individuals have a high frequency of virus-specific cytotoxic T lymphocytes (CTLs) that effectively reduces the viral load. However, the CTLs are unable to clear the virus at later stages of infection, leading to disease progression. Dysregulation of cytokines like interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) as a result of the interaction of HIV-1-specific T cells with antigen-presenting cells is one of the possible causes of CTL dysfunction. Secretion of IL-12 is reduced with the progression of HIV infection, correlating with impaired CTL function; however, the role of IL-12 in CTL regulation awaits elucidation. Here, we have studied the role of IL-12 in CTL dysfunction by using DNA immunization of wild-type (WT) and IL-12-deficient mice with HIV-1 gp120 complementary DNA. It was observed that the CTL response in IL-12-deficient mice was significantly less than that in WT mice. Our results further demonstrated that coimmunization with IL-12 vector restored the impaired CTL response in IL-12-deficient mice. However, immunization with IL-12 vector failed to rescue the CTL response in IFN-gamma deficient mice, suggesting that the CTL-promoting function of IL-12 is IFN-gamma-mediated. Our data suggest a phase-specific role of IL-12 in the CTL response, specifically in the priming of CD4+ T cells that provide help to CD8+ T cells. Our results also suggest that IL-12 is vital for the priming of antigen-specific T cells and plays an essential role in IFN-gamma induction in T cells.