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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2699-2704.
Prepublished online as a Blood First Edition Paper on December 18, 2003; DOI 10.1182/blood-2003-06-1913.


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IMMUNOBIOLOGY

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

JoAnn Castelli, Elaine K. Thomas, Michel Gilliet, Yong-Jun Liu, and Jay A. Levy

From the Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco, San Francisco, CA; and DNAX, Palo Alto, CA.

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. (Blood. 2004;103:2699-2704)


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