COSTIMULATION VIA TCR AND IL-1 RECEPTOR REVEALS A NOVEL IL-1-ALPHA-MEDIATED AUTOCRINE PATHWAY OF TH2 CELL-PROLIFERATION

Citation
M. Huber et al., COSTIMULATION VIA TCR AND IL-1 RECEPTOR REVEALS A NOVEL IL-1-ALPHA-MEDIATED AUTOCRINE PATHWAY OF TH2 CELL-PROLIFERATION, The Journal of immunology, 160(9), 1998, pp. 4242-4247
Citations number
26
Categorie Soggetti
Immunology
Journal title
ISSN journal
00221767
Volume
160
Issue
9
Year of publication
1998
Pages
4242 - 4247
Database
ISI
SICI code
0022-1767(1998)160:9<4242:CVTAIR>2.0.ZU;2-0
Abstract
Previous studies have shown that triggering of Th2 cells via the TCR i s sufficient for production of IL-4 but not for proliferation of these cells. Proliferation of Th2 cells occurs only in the additional prese nce of a costimulatory signal delivered by IL-1. For the majority of T h2 cell clones, this type of proliferation was found to be independent of IL-4, Here, we further investigated the mechanism of IL-4-independ ent proliferation. We demonstrate that, after costimulation via TCR an d IL-1R, but not via either receptor alone, Th2 cells are triggered to produce cell-associated IL-1 alpha, as detected at the level of funct ion, protein, and mRNA expression, In the presence of the TCR signal, autocrine IL-1 alpha is then able to costimulate IL-4-independent prol iferation of Th2 cells and to further enhance its own production. Thus , our results point to a novel, IL-4-independent, self-amplifying auto crine pathway of Th2 cell proliferation that requires a signal via the TCR and a costimulatory signal via IL-1R. This pathway may explain fr ustrating results in experimental models that attempted to treat estab lished Th2-mediated diseases in vivo with IL-4-neutralizing agents alo ne.