Semaphorin 4A Enhances T Cell Activation

Science's STKE  15 Oct 2002:
Vol. 2002, Issue 154, pp. tw377-TW377
DOI: 10.1126/stke.2002.154.tw377

Semaphorins, originally identified as axon guidance regulators in the nervous system, are also involved in various aspects of immune cell function (see Bismuth and Boumsell). Kumanagoh et al. report that Sema 4A enhanced T cell activation, measured as proliferation and stimulation of interleukin and interferon production, in vitro and in vivo. In a mouse model of autoimmune encephalomyelitis (EAE), EAE was suppressed if the mice were injected with an antibody against Sema 4A. The Tim-2 protein, a member of a family of proteins expressed on T cells that contain immunoglobulin and mucin domains, was identified by expression cloning as a receptor for Sema 4A. Unlike the CD100 (also known as Sema 4D), Sema 4A stimulated tyrosine phosphorylation of Tim-2 in transfected COS7 cells--CD100 promotes dephosphorylation of its receptor CD72.

G. Bismuth, L. Boumsell, Controlling the immune system through semaphorins. Science's STKE (2002),;2002/128/re4. [Abstract] [Full Text]

A. Kumanogoh, S. Marukawa, K. Suzuki, N. Takegahara, C. Watanabe, E. Ch'ng, I. Ishida, H. Fujimura, S. Sakoda, K. Yoshida, H. Kikutani, Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2. Nature 419, 629-633 (2002). [Online Journal]