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
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.