Burmeister Y, Lischke T, Dahler AC, Mages HW, Lam KP, Coyle AJ, Kroczek RA, Hutloff A (2008): ICOS controls the pool size of effector-memory and regulatory T cells
J. Immunol. 180 (2): 774-782.
ICOS is an important regulator of T cell effector function. ICOS-deficient patients as well as knockout mice show severe defects in T cell-dependent B cell responses. Several in vitro and in vivo studies attributed this phenomenon to impaired up-regulation of cell surface communication molecules and cytokine synthesis by ICOS-deficient T cells. However, we now could show with Ag-specific T cells in a murine adoptive transfer system that signaling via ICOS does not significantly affect early T cell activation. Instead, ICOS substantially contributes to the survival and expansion of effector T cells upon local challenge with Ag and adjuvant. Importantly, the observed biological function of ICOS also extends to FoxP3+ regulatory T cells, as can be observed after systemic Ag delivery without adjuvant. In line with these findings, absence of ICOS under homeostatic conditions of nonimmunized mice leads to a reduced number of both effector-memory and FoxP3+ regulatory T cells. Based on these results, we propose a biological role for ICOS as a costimulatory, agonistic molecule for a variety of effector T cells with differing and partly opposing functional roles. This concept may reconcile a number of past in vivo studies with seemingly contradictory results on ICOS function.
see also:
Burmeister Y; Lischke T; Dahler AC; Mages HW; Lam KP; Coyle AJ; Kroczek RA; Hutloff A (2008): ICOS controls the pool size of effector-memory and regulatory T cells (vol 180, pg 774, 2008). J. Immunol. 180 (5): 3613 /MAR 1 2008/Article; Errata