ICOS is critical for T helper cell?mediated lung mucosal inflammatory responses.

We examined the requirement for and cooperation between CD28 and inducible costimulator (ICOS) in effective T helper (T_H) cell responses in vivo. We found that both CD28 and ICOS were critical in determining the outcome of an immune response; cytolytic T lymphocyte?associated antigen 4?immunoglobulin (CTLA-4?Ig), ICOS-Ig and/or a neutralizing ICOS monoclonal antibody attenuated T cell expansion, T_H2 cytokine production and eosinophilic inflammation. CD28-dependent signaling was essential during priming, whereas ICOS?B7RP-1 regulated T_H effector responses, and the up-regulation of chemokine receptors that determine T cell migration. Our data suggests a scenario whereby both molecules regulate the outcome of the immune response but play separate key roles: CD28 primes T cells and ICOS regulates effector responses. [ABSTRACT FROM AUTHOR]