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 a n immune response; cytolytic T lymphocyte-associated antigen 4-immunoglobul in (CTLA-4-Ig), ICOS-Ig and/or a neutralizing ICOS monoclonal antibody atte nuated T cell expansion, T(H)2 cytokine production and eosinophilic inflamm ation. CD28-dependent signaling was essential during priming, whereas ICOS- B7RP-I regulated T-H effector responses, and the up-regulation of chemokine receptors that determine T cell migration. Our data suggests a scenario wh ereby both molecules regulate the outcome of the immune response but play s eparate key roles: CD28 primes T cells and ICOS regulates effector response s.