Interleukin-15: Multiple roles in controlling HIV infection in chimpanzees (B143)

Abstract

Abstract We have recently shown that Interleukin-15 (IL-15) plays a crucial role in eliciting interferon-gamma (IFN-γ) production from CD3−CD8+ NK cells in HIV infected chimpanzees (Pan troglodytes). CD3−CD8+ IFN-γ+ NK cells were consistently higher than CD3+CD8+ IFN-γ+ T cells and CD3−CD56+ IFN-γ+ NK cells by flow cytometry analysis. Accordingly, these findings prompted further investigation into the role of IL-15 during HIV infection. Analysis of fresh chimpanzee leukocytes revealed that a rare subpopulation of T cells express surface IL-15. HIV infected chimpanzees were shown express surface IL-15 on < 1 % to 3 % of T cells. Multiparameter flow cytometry analysis utilizing a whole blood system demonstrated that the cells were CD3+CD4+CD16+IL15+ and CD3+CD8+CD16+IL15+ T cells. These populations were shown to be CD25 negative, however, in vitro stimulation of PBMCs with interleukin-15 resulted in upregulation CD4+CD25+ T cells. Additional blood specimens from HIV infected chimpanzees examined during routine physicals also exhibited CD3−CD8+ IFN-γ+ NK cells > CD3+CD8+ IFN-γ+ T cells (p< 0.009, n=10). Research has shown that CD8+ lymphocytes play a substantial role in controlling HIV replication and declining CD4 cells leads to an increase in susceptibility to pathogens. During this study IL-15 was also shown to induce IFN-γ and TNF-α expression from this CD3−CD8+ NK cells. These findings provide additional insights on the influence of IL-15 and chimpanzee resistance mechanisms during HIV infection.