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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- 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.

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