| Autor: |
Mathieu Gigoux, Jijun Sháng, Pak, Youngshil, Minghong Xu, Choe, Jongseon, Mak, Tak W., Suh, Woong-Kyung |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 12/1/2009, Vol. 106 Issue 48, p20371-20376, 6p |
| Abstrakt: |
The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS). are required for the generation of follicular B helper T cells (TFH) and germinal center (GC) reaction. A common signal transducer used by CD28 and ICOS is the phosphoinositide 3-kinase (Pl3K). Although it is known that CD28-mediated Pl3K activation is dispensable for GC reaction, the role of ICOS-driven Pl3K signaling has not been defined. We show here that knock-in mice that selectively lost the ability to activate Pl3K through ICOS had severe defects in TFH generation, GC reaction, antibody class switch, and antibody affinity maturation. In preactivated CD4+ T cells, ICOS delivered a potent Pl3K signal that was critical for the induction of the key TFH cytokines, IL-21 and IL-4. Under the same settings, CD28 was unable to activate Pl3K but supported a robust secondary expansion of T cells. Thus, our results demonstrate a nonredundant function of ICOS-PI3K pathway in the generation of TFH and suggest that CD28 and ICOS play differential roles during a multistep process of TFH differentiation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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