Nonredundant roles of Sema4A in the immune system: defective T cell priming and Th1/Th2 regulation in Sema4A-deficient mice.


The class IV semaphorin Sema4A provides a costimulatory signal to T cells. To investigate the possible developmental and regulatory roles of Sema4A in vivo, we generated Sema4A-deficient mice. Although Sema4A-deficient mice develop normally, DCs and T cells from knockout mice display poor allostimulatory activities and T helper cell (Th) differentiation, respectively. Interestingly, in addition to its expression on DCs, Sema4A is upregulated on Th1-differentiating cells, and it is necessary for in vitro Th1 differentiation and T-bet expression. Consequently, in vivo antigen-specific T cell priming and antibody responses against T cell-dependent antigens are impaired in the mutant mice. Additionally, Sema4A-deficient mice exhibit defective Th1 responses. Furthermore, reconstitution studies with antigen-pulsed DCs reveal that DC-derived Sema4A is important for T cell priming, while T cell-derived Sema4A is involved in developing Th1 responses. Collectively, these results indicate a nonredundant role of Sema4A not only in T cell priming, but also in the regulation of Th1/Th2 responses.

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@article{Kumanogoh2005NonredundantRO, title={Nonredundant roles of Sema4A in the immune system: defective T cell priming and Th1/Th2 regulation in Sema4A-deficient mice.}, author={Atsushi Kumanogoh and Takashi Shikina and Kazuhiro Suzuki and Satoshi Uematsu and Kazunori Yukawa and Shin-ichiro Kashiwamura and Hiroko Tsutsui and Midori Yamamoto and Hyota Takamatsu and Elizabeth P Ko-Mitamura and Noriko Takegahara and Satoko Marukawa and Isao Ishida and Hiroshi Morishita and Durbaka V. R. Prasad and Manabu Tamura and Masayuki Mizui and Toshihiko Toyofuku and Shizuo Akira and Kiyoshi Takeda and Masaru Okabe and Hitoshi Kikutani}, journal={Immunity}, year={2005}, volume={22 3}, pages={305-16} }