First Author | Kumanogoh A | Year | 2005 |
Journal | Immunity | Volume | 22 |
Issue | 3 | Pages | 305-16 |
PubMed ID | 15780988 | Mgi Jnum | J:97027 |
Mgi Id | MGI:3574161 | Doi | 10.1016/j.immuni.2005.01.014 |
Citation | Kumanogoh A, et al. (2005) Nonredundant Roles of Sema4A in the Immune System: Defective T Cell Priming and Th1/Th2 Regulation in Sema4A-Deficient Mice. Immunity 22(3):305-16 |
abstractText | 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. |