IL-15 ex vivo overcomes CD4+ T cell deficiency for the induction of human antigen-specific CD8+ T cell responses

Abstract

CD4+ Th cells are important for the induction and maintenance of antigen-specific CD8+ T cell function, so their loss or dysfunction in HIV-infected or cancer patients could reduce the patients' ability to control viral infection. Previous work in murine systems indicated that IL-15 codelivered with vaccines could overcome CD4+ Th cell deficiency for induction of functionally efficient CD8+ T cells and maintenance of viral-specific CTLs, but its efficacy in helping primary human CD8+ T cell responses is unknown. In the present study, a peptide-pulsed, DC-based human coculture ex vivo system was used to study the role of IL-15 in overcoming CD4+ Th deficiency to elicit CD8+ T cell responses in CD4-depleted PBMCs from healthy individuals and PBMCs from HIV-1-infected patients. We found that IL-15 could overcome CD4+ Th deficiency to induce primary and recall memory CD8+ T cell responses in healthy individuals. Moreover, in CD4-deficient, HIV-1-infected patients with diminished CD8+ T cell responses, IL-15 greatly enhanced CD8+ T cell responses to alloantigen. These results suggest that IL-15 may be useful in the development of therapeutic and preventive vaccines against cancers and viral infections in patients defective in CD4+ Th cell.