Journal
NATURE IMMUNOLOGY
Volume 2, Issue 7, Pages 597-604Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/89739
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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(H)2 cytokine production and eosinophilic inflammation. 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 whereby both molecules regulate the outcome of the immune response but play separate key roles: CD28 primes T cells and ICOS regulates effector responses.
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