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 long-term 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 interleukin-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.
Castelli
JoAnn
J
Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco 94143-1270, USA.
Thomas
Elaine K
EK
Gilliet
Michel
M
Liu
Yong-Jun
YJ
Levy
Jay A
JA
D017252:CD3 Complex / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology* / Q000627:therapeutic use; D012016:Reference Values
D017252:CD3 Complex; D016827:CD8 Antigens; D016207:Cytokines; D019409:Interleukin-15