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CUTTING EDGE |
Department of Biology, Inflammation Division, Millennium Pharmaceuticals, Cambridge, MA 02139
Optimal T cell activation requires engagement of CD28 with its
counterligands B7-1 and B7-2. Inducible costimulator (ICOS) is the
third member of the CD28/CTLA4 family that binds a B7-like protein,
B7RP-1. Administration of ICOS-Ig attenuates T cell expansion following
superantigen (SAg) administration, but fails to regulate either
peripheral deletion or anergy induction. ICOS-Ig, but not CTLA4-Ig,
uniquely regulates SAg-induced TNF-
production, whereas IL-2
secretion is modulated by CTLA4-Ig, but not ICOS-Ig. In contrast, both
ICOS and CD28 are required for complete attenuation of IL-4 production.
Our data suggest that ICOS and CD28 regulate T cell expansion and that
ligation of either CD28 or ICOS can either uniquely regulate cytokine
production (IL-2/TNF-) or synergize for optimal cytokine production
(IL-4) after SAg administration.
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