ICOS controls the pool size of effector-memory and regulatory T cells.

TY - JOUR

T1 - ICOS controls the pool size of effector-memory and regulatory T cells.

AU - Burmeister, Yvonne

AU - Lischke, Timo

AU - Dahler, Anja C

AU - Mages, Hans Werner

AU - Lam, Kong-Peng

AU - Coyle, Anthony J

AU - Kroczek, Richard A

AU - Hutloff, Andreas

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Animals

KW - Mice

KW - Mice, Knockout

KW - Apoptosis

KW - Cell Count

KW - T-Lymphocytes, Regulatory/immunology

KW - Immunologic Memory

KW - Thymus Gland/immunology

KW - Antigens, Differentiation, T-Lymphocyte/genetics/metabolism

KW - Inducible T-Cell Co-Stimulator Protein

KW - Lymphocyte Activation

KW - Animals

KW - Mice

KW - Mice, Knockout

KW - Apoptosis

KW - Cell Count

KW - T-Lymphocytes, Regulatory/immunology

KW - Immunologic Memory

KW - Thymus Gland/immunology

KW - Antigens, Differentiation, T-Lymphocyte/genetics/metabolism

KW - Inducible T-Cell Co-Stimulator Protein

KW - Lymphocyte Activation

M3 - SCORING: Journal article

VL - 180

SP - 774

EP - 782

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 2

M1 - 2

ER -