Mature dendritic cells can enhance CD8+ cell noncytotoxic anti-HIV responses:: the role of IL-15

The CD8(+) cell noncytotoxic anti-HIV response (CNAR) Is associated with a longterm healthy clinical state in HIV-infected individuals. Over time CNAR is reduced concomitant with progression to disease. In studies to evaluate whether the interaction between CD8(+) cells and dendritic cells (DCs) could increase CNAR, CD8(+) cells from individuals who showed a decrease in this antiviral activity were cocultured with monocyte-derived dendritic cells matured with CD40 ligand. After coculture with these mature DCs, the CD8(+) cells showed an increase in CNAR greater than that observed with CD8(+) cells costimulated with CD3/CD28 antibodies. This antiviral response appeared to be mediated primarily by production of interieukin-15 (IL-15) by the mature DCs. Purified IL-15 also enhanced CNAR, whereas IL-12 showed no substantial effect. These studies provide another potential approach by which the immune system in HIV infection could be restored by cytokine therapy, particularly IL-15 administration. (C) 2004 by The American Society of Hematology.