Trends in Immunology
Teaching tired T cells to fight HIV: time to test IL-15 for immunotherapy?
Section snippets
IL-15 production during HIV infection
The damage to normal cytokine signaling and function is a key factor in the immunopathogenesis of HIV infection [13]. The perturbation of the cytokine network contributes both to the impairment of HIV-specific immune responses and to the increased susceptibility to opportunistic infections. Type 1 cytokines, generally, are decreased with the progression of HIV disease, whereas type 2 cytokines are increased. However, some authors have shown that there are no detectable shifts from Th1 to Th2
IL-15 as an immunotherapeutic agent in HIV infection
The ability of IL-15 to modulate innate and specific immune responses against HIV supports the clinical interest in using this cytokine as an immunorestorative agent during HIV infection (Figure 1). HIV-specific CD8+ T-cell responses have a central role in controlling HIV infection and disease progression. Recent data indicate that NK cells are able to control HIV replication to the same extent as CD8+ T cells [27]. In HIV-infected individuals, in vitro treatment with IL-15 improves neutrophil
IL-15 and immune control of HIV infection
Although several studies suggest that the immune system has an important role in the response against HIV, the virus persists in the host, leading to disease progression and the development of AIDS. The reasons for a lack of effective immune control are still not completely understood. Several factors, including immune exhaustion, replicative senescence of CD8+ T cells, lack of adequate Th-cell function, immune escape, ineffective cytotoxic T-lymphocyte (CTL) responses in vivo and viral
Concluding remarks
The defective production of IL-15 in HIV-infected individuals might contribute to the impairment of NK and CD8+ T-cell function. In vitro administration of IL-15 inhibits CD95 (Fas)-induced apoptosis and enhances the survival and function of HIV-specific CD8+ T cells, indicating the importance of this cytokine in the restoration of HIV-specific immunity. In addition, IL-15 seems to be more potent than IL-2 and IL-7 in augmenting CD8+ T-cell responses. Because of its long-lasting effect on
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