Inducible Costimulator Promotes Helper T-cell Differentiation Through Phosphoinositide 3-kinase

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2009 Nov 17

PMID 19915142

Citations 125

Authors

Mathieu Gigoux

Jijun Shang

Youngshil Pak

Minghong Xu

Jongseon Choe

Tak W Mak

Woong-Kyung Suh

Affiliations

Soon will be listed here.

Abstract

The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (T(FH)) and germinal center (GC) reaction. A common signal transducer used by CD28 and ICOS is the phosphoinositide 3-kinase (PI3K). Although it is known that CD28-mediated PI3K activation is dispensable for GC reaction, the role of ICOS-driven PI3K signaling has not been defined. We show here that knock-in mice that selectively lost the ability to activate PI3K through ICOS had severe defects in T(FH) generation, GC reaction, antibody class switch, and antibody affinity maturation. In preactivated CD4(+) T cells, ICOS delivered a potent PI3K signal that was critical for the induction of the key T(FH) cytokines, IL-21 and IL-4. Under the same settings, CD28 was unable to activate PI3K but supported a robust secondary expansion of T cells. Thus, our results demonstrate a nonredundant function of ICOS-PI3K pathway in the generation of T(FH) and suggest that CD28 and ICOS play differential roles during a multistep process of T(FH) differentiation.

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