Editors' ChoiceImmunology

Stimulatory Effects of ICOS

Science's STKE  09 Jan 2001:
Vol. 2001, Issue 64, pp. tw9
DOI: 10.1126/stke.2001.64.tw9

T cell activation is thought to require two events: engagement of the T cell receptor with antigen that is presented on the surface of an antigen-presenting cell (APC), and costimulatory signals that involve engagement of other molecule pairs between the T cell and the APC. One such costimulatory pair is the inducible costimulatory molecule (ICOS) present on T cells and its ligand B7HRP-1. Three groups have analyzed the contribution of this interaction to immune function in vivo by generating ICOS-null mice. ICOS-deficient mice exhibited defects in T cell activation and proliferation, failing to produce critical cytokines including interleukins 2 and 4. The absence of ICOS also impaired the ability of T cells to direct the appropriate humoral response to antigens, indicating its importance in promoting T cell-B cell collaboration. The findings are summarized by Schwartz, who suggests that this costimulatory molecule has important implications in allergic reactions and the inflammatory response in humans.

Dong, C., Juedes, A.E., Temann, U.-A., Shresta, S., Allison, J.P., Ruddle, N.H., and Flavell, R.A. (2000) ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature 409: 97-101. [Online Journal]

McAdam, A.J., Greenwald, R.J., Levin, M.A., Chernova, T., Malenkovich, N., Ling, V., Freeman, G.J., and Sharpe, A.H. (2000) ICOS is critical for CD40-mediated antibody class switching. Nature 409: 102-105. [Online Journal]

Tafuri, A., Shahinian, A., Bladt, F., Yoshinaga, S.K., Jordana, M., Wakeham, A., Boucher, L.-M., Bouchard, D., Chan, V.S.F., Duncan, G., Odermatt, B., Ho, A., Itie, A., Horan, T., Whoriskey, J.S., Pawson, T., Penninger, J.M., Ohashi, P.S., and Mak, T.W. (2000) ICOS is essential for effective T-helper-cell responses. Nature 409: 105-109. [Online Journal]

Schwartz, R.H. (2000) It takes more than two to tango. Nature 409: 31-32. [Online Journal]