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Requirement for the Lymphocyte Semaphorin, CD100, in the Induction of Antigen-Specific T Cells and the Maturation of Dendritic Cells¹

Atsushi Kumanogoh^2,*, Kazuhiro Suzuki^2,*, EweSeng Ch’ng^*, Chie Watanabe^*, Satoko Marukawa^*, Noriko Takegahara^*, Isao Ishida^*, Takehito Sato, Sonoko Habu, Kanji Yoshida^*, Wei Shi^* and Hitoshi Kikutani^3,*

^* Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; and Department of Immunology, Tokai University, Isehara, Japan

CD100 belongs to the semaphorin family, several members of which are known to act as repulsive axonal guidance factors during neuronal development. We have previously demonstrated that CD100 plays a crucial role in humoral immunity. In this study, we show that CD100 is also important for cellular immunity through the maturation of dendritic cells (DCs). CD100^-/- mice fail to develop experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein peptide, because myelin oligodendrocyte glycoprotein-specific T cells are not generated in the absence of CD100. In vitro studies with T cells from OVA-specific TCR-transgenic mice demonstrate that Ag-specific T cells lacking CD100 fail to differentiate into cells producing either IL-4 or IFN- in the presence of APCs and OVA peptide. In addition, DCs from CD100^-/- mice display poor allostimulatory capabilities and defects in costimulatory molecule expression and IL-12 production. The addition of exogenous soluble rCD100 restores normal functions in CD100^-/- DCs and further enhances functions of normal DCs. Furthermore, treatment of Ag-pulsed DCs with both soluble CD100 and anti-CD40 before immunization significantly enhances their immunogenicity. This treatment elicits improved T cell priming in vivo, enhancing both primary and memory T cell responses. Collectively, these results demonstrate that CD100, which enhances the maturation of DCs, is essential in the activation and differentiation of Ag-specific T cells.

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