title: 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.
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Yu
authors.forename: Abdul
authors.initials: A
authors.lastname: Tawab-Amiri
authors.forename: Amiran
authors.initials: A
authors.lastname: Dzutsev
authors.forename: Marianna
authors.initials: M
authors.lastname: Sabatino
authors.forename: Karen
authors.initials: K
authors.lastname: Aleman
authors.forename: Robert
authors.initials: R
authors.lastname: Yarchoan
authors.forename: Masaki
authors.initials: M
authors.lastname: Terabe
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Sui
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*
chemical_list: D019409:Interleukin-15