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The Journal of Immunology, 2005, 174: 5959-5967.
Copyright © 2005 by The American Association of Immunologists

CD4+CD25+ Regulatory T Cells Attenuate the Phosphatidylinositol 3-Kinase/Akt Pathway in Antigen-Primed Immature CD8+ CTLs during Functional Maturation 1

Hidefumi Kojima2, Yumiko Kanno, Hidenori Hase and Tetsuji Kobata

Department of Immunology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan

This study was designed to determine the role of CD25+CD4+ regulatory T (Tr) cells in CTL maturation and effector functions using a murine CTL line and in vitro MLC. Tr cells inhibited CTL functional maturation, but had no effect on CTL effector functions. In CD4+ responder T cell-depleted MLC supplemented with IL-2, Tr cells suppressed mature CTL generation only when added within the first 2 days of culture. Tr cells down-regulated levels of active Akt, but not STAT5 or ZAP70 in Ag-primed immature CTLs. Down-regulation of active Akt was accompanied by a reduction in CTL cell size and IL-2R{alpha} expression. In Tr cell-depleted MLC, CTLs were generated that exhibited high levels of nonspecific cytotoxicity. Our in vitro findings suggest that Tr cells regulate functional CTL maturation to generate optimal Ag-specific immune responses through the control of the PI3K/Akt pathway.




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