Abstract
T cell activation, differentiation and effector functions depend on signals delivered through the antigen‐specific TCR and non‐clonal costimulatory receptors on the T cell. Activated T cells express the inducible costimulator (ICOS). We examined the co‐expression of ICOS with Th cytokines in mucosal immune responses. ICOS^+^CD4^+^ Th cells expressed strikingly different cytokines depending on the type of infection encountered and the cells' anatomical localization. In the Th2‐dominated response to Schistosoma mansoni, ICOS expression of CD4^+^ cells isolated from the liver was strongly associated with the expression of IL‐5, IL‐10, IL‐13, and T1/ST2, but not with the chemokine receptor CXCR5, a pattern consistent with Th2 effector cells. In the secondary lymphatic organs of schistosome‐infected mice, ICOS expression was randomly correlated with Th2 effector‐cytokines, but positively correlated with CXCR5 expression; a pattern consistent with follicular Th cells. In Th cells isolated from gut or liver of mice infected with Toxoplasma gondii, ICOS expression was positively correlated with IFN‐γ production. Finally, in the severe combined immunodeficiency transfer colitis model, ICOS expression was strongly positively associated with IFN‐γ and IL‐2. Thus, ICOS appears to costimulate distinct effector functions in different immune responses, depending on factors such as the nature of the antigen encountered and localization and chronicity of the immune response.