Augmentation of effector CD8+ T cell generation with enhanced granzyme B expression by IL-27.
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-12Rbeta2, 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-12Rbeta2, 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-12Rbeta2, 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.
Morishima
Noriko
N
Intractable Immune System Disease Research Center, Tokyo Medical University, Tokyo, Japan.
Owaki
Toshiyuki
T
Asakawa
Masayuki
M
Kamiya
Sadahiro
S
Mizuguchi
Junichiro
J
Yoshimoto
Takayuki
T
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000276:immunology / Q000517:prevention & control; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D053804:Granzymes; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology; D007378:Interleukins / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008894:Milk Proteins / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053707:Receptors, Interleukin-12; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D050799:STAT5 Transcription Factor; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D020825:T-Box Domain Proteins; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis; D014162:Transfection; D000098815:T-bet Transcription Factor
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; C486767:Il27 protein, mouse; D007378:Interleukins; D008562:Membrane Glycoproteins; D008894:Milk Proteins; D052899:Pore Forming Cytotoxic Proteins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D050799:STAT5 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; C494091:Stat4 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D054353:Perforin; D018664:Interleukin-12; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases