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Costimulation by extracellular matrix proteins determines the response to TCR ligation.

Abstract：

:Although ligation of the T-cell antigen receptor (TCR) is central to the responsiveness and antigen specificity of T-cells, it is insufficient to elicit a response. To determine whether the need for costimulation reflects inadequate strength of signal transduction through the TCR or an absolute block of signaling in the absence of a coligand, we studied T-cell activation under serum-free conditions eliminating costimulation by various extracellular matrix proteins which otherwise have an omnipresent and frequently overlooked effect. Engagement of the TCR leads to induction of Fas, but not to measurable IL-2 secretion or apoptosis. Those activation parameters are induced by costimulation through integrin alphaVbeta3. Furthermore, T-cell survival or elimination is determined by the type of ligand binding to this coreceptor with vitronectin, fibronectin, and fibrinogen efficiently inducing apoptosis and IL-2 production while osteopontin and entactin mediate IL-2 secretion comparably without causing programmed cell death. Consistent with the cytokine properties of these ligands, differential costimulation depends on their presentation in soluble rather than immobilized form. The determination of elimination versus survival of activated T-cells by coligation of beta3-integrins may have bearing on the fundamental postthymic mechanisms that shape the T-cell repertoire.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Adler B,Ashkar S,Cantor H,Weber GF

doi

10.1006/cimm.2001.1800

subject

Has Abstract

pub_date

2001-05-25 00:00:00

pages

30-40

issue

1

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(01)91800-3

journal_volume

210

pub_type

杂志文章

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