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Blood, 1 October 2001, Vol. 98, No. 7, pp. 2143-2151

IMMUNOBIOLOGY

Interleukin-10 promotes the maintenance of antitumor CD8+ T-cell effector function in situ

Shin-ichiro Fujii, Kanako Shimizu, Takashi Shimizu, and Michael T. Lotze

From the Department of Surgery, University of Pittsburgh School of Medicine, and the Division of Biological Therapeutics, University of Pittsburgh Cancer Institute, PA.

Interleukin-10 (IL-10) is a multifunctional cytokine that can exert suppressive and stimulatory effects on T cells. It was investigated whether IL-10 could serve as an immunostimulant for specific CD8+ cytotoxic T cell (CTL) in vivo after vaccination and, if so, under what conditions. In tumor prevention models, administration of IL-10 before, or soon after, peptide-pulsed primary dendritic cell immunization resulted in immune suppression and enhanced tumor progression. Injection of IL-10, however, just after a booster vaccine significantly enhanced antitumor immunity and vaccine efficacy. Analysis of spleen cells derived from these latter animals 3 weeks after IL-10 treatment revealed that the number of CD8+ CD44hi CD122+ T cells had increased and that antigen-specific proliferation in vitro was enhanced. Although cytotoxicity assays did not support differences between the various treatment groups, 2 more sensitive assays measuring antigen-specific interferon-gamma production at the single-cell level demonstrated increases in the number of antigen-specific responder T cells in animals in the vaccine/IL-10 treatment group. Thus, IL-10 may maintain the number of antitumor CD8+ T cells. In adoptive transfer studies, the ability of IL-10 to maintain CTL function could be enhanced by the depletion of CD4+ T cells. This suggests that IL-10 mediates contrasting effects on both CD4+ and CD8+ T cells that result in either immune dampening or immune potentiation in situ, respectively. Appreciation of this dichotomy in IL-10 immunobiology may allow for the design of more effective cancer vaccines designed to activate and maintain specific CD8+ T-cell effector function in situ.

© 2001 by The American Society of Hematology.
 

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