Contrasting Effects of Low-Dose IL-2 on Vaccine-Boosted Simian Immunodeficiency Virus (SIV)-Specific CD4+ and CD8+ T Cells in Macaques Chronically Infected with SIVmac251.

摘要

IL-2, the first cytokine discovered with T cell growth factor activity, is now known to have pleiotropic effects on T cells. For example, it can promote growth, survival, and differentiation of Ag-selected cells, or facilitate Ag-induced cell death of T cells when Ag persists, and in vivo, it is thought to contribute to the regulation of the size of adaptive T cell response. IL-2 is deficient in HIV-1 infection and has been used in the management of HIV-1-infected individuals undergoing antiretroviral therapy. In this study, we investigated how continuous low-dose IL-2 affected the CD4(+) and CD8(+) T cell response induced by two inoculations of a canarypox recombinant SIV-based vaccine candidate in healthy macaques chronically infected with SIVmac251. These macaques had normal levels of CD4(+) T cells at the beginning of antiretroviral therapy treatment. Vaccination in the presence of IL-2 significantly augmented Gag-specific CD8(+) T cell responses, but actually reduced Gag-specific CD4(+) T cell responses. Although IL-2 at low doses did not change the overall concentration of circulating CD4(+) or CD8(+) T cells, it expanded the frequency of CD4(+)CD25(+) T cells. Depletion of the CD4(+)CD25(+) T cells in vitro, however, did not result in a reconstitution of Gag-specific CD4(+) responses or augmentation of SIV-specific CD8(+) T cell responses. Thus, we conclude that the decrease in virus-specific CD4(+) T cell response may be due to IL-2-promoted redistribution of cells from the circulation, or due to Ag-induced cell death, rather than suppression by a T regulatory population.