Role of IL-12 in HIV infection and vaccine

Among cytokines that dictate the fate of developing immune responses, IL-12 represents an important nexus for the development of type I cell-mediated immune responses (CMI). This factor is primarily produced by monocytic cell lineages in response to stimuli such as pathogen-associated molecular patterns, dictating the development of naive T cells as they differentiate into antigen-specific T cells. HIV infection results in an early loss of effective TH1 prototype CMI when such responses appear to be precisely the type of CMI needed to control the virus and a host of opportunistic pathogens. Besides CD4 T cell loss, much of the muted IL-12 response has been attributed to direct effects of HIV or its proteins on antigen-presenting cells, while T and NK cell responses to IL-12 appear maintained during chronic HIV infection. However, while IL-12 therapy is unlikely to provide major benefits in the context of an established HIV infection, IL-12 preconditioning of monkeys during acute SIV infection markedly delayed disease progression. These findings suggest that IL-12 may serve as a critical vaccine adjuvant, and as treatment for particular opportunistic agents or neoplasm such as Kaposi's sarcoma; it has already shown promising results in the context of HIV infection.