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The Journal of Immunology, 2005, 175: 1686-1693.
Copyright © 2005 by The American Association of Immunologists

Augmentation of Effector CD8+ T Cell Generation with Enhanced Granzyme B Expression by IL-27 1

Noriko Morishima*,{dagger}, Toshiyuki Owaki*,{ddagger}, Masayuki Asakawa*,{dagger}, Sadahiro Kamiya*,{dagger}, Junichiro Mizuguchi*,{dagger} and Takayuki Yoshimoto2,*

* Intractable Immune System Disease Research Center and {dagger} Department of Immunology, Tokyo Medical University, Tokyo, Japan; and {ddagger} Department of Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan

IL-27 is a novel IL-12 family member that plays a role in the early regulation of Th1 initiation. We have recently demonstrated that IL-27 has a potent antitumor activity, which is mainly mediated through CD8+ T cells, and also has an adjuvant activity to induce epitope-specific CTL in vivo. In this study, we further investigated the in vitro effect of IL-27 on CD8+ T cells of mouse spleen cells. In a manner similar to CD4+ T cells, IL-27 activated STAT1, -2, -3, -4, and -5, and augmented the expression of T-bet, IL-12R{beta}2, and granzyme B, and slightly that of perforin in naive CD8+ T cells stimulated with anti-CD3. IL-27 induced synergistic IFN-{gamma} production with IL-12 and proliferation of naive CD8+ T cells. Moreover, IL-27 enhanced proliferation of CD4+ T cell-depleted spleen cells stimulated by allogeneic spleen cells and augmented the generation of CTL. In STAT1-deficient naive CD8+ T cells, IL-27-induced proliferation was not reduced, but synergistic IFN-{gamma} production with IL-12 was diminished with decreased expression of T-bet, IL-12R{beta}2, granzyme B, and perforin. In T-bet-deficient naive CD8+ T cells, IL-27-induced proliferation was hardly reduced, but synergistic IFN-{gamma} production with IL-12 was diminished with decreased expression of IL-12R{beta}2, granzyme B, and perforin. However, IL-27 still augmented the generation of CTL from T-bet-deficient CD4+ T cell-depleted spleen cells stimulated by allogeneic spleen cells with increased granzyme B expression. These results suggest that IL-27 directly acts on naive CD8+ T cells in T-bet-dependent and -independent manners and augments generation of CTL with enhanced granzyme B expression.




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