Murine T helper cell-2 lymphocytes express type I and type II IL-1 receptors, but only the type I receptor mediates costimulatory activity
McKean, D.J.; Podzorski, R.P.; Bell, M.P.; Nilson, A.E.; Huntoon, C.J.; Slack, J.; Dower, S.K.; Sims, J.
Journal of Immunology 151(7): 3500-3510
1993
ISSN/ISBN: 0022-1767 PMID: 8376789 Document Number: 415309
The role of IL-1 in augmenting the Ag receptor-initiated activation program was evaluated in IL-4-producing (Th2) CD4+ murine T lymphocytes. Northern blot and 125I-labeled IL-1-alpha cross-linking analyses demonstrated that Th2 lymphocytes express both type I and type II IL-1R. The expression of both IL-1R isoforms on the surface of the Th2 cells is coordinately up-regulated in response to anti-CD3 cross-linking in the absence of detectable accessory cells. Analyses of the kinetics of IL-1R acquisition demonstrated that the peak level of type I and type II IL-1R mRNA expression occurs after the peak expression of mRNA encoding IL-2R-alpha and IL-4, which are two IL-1 -responsive events in the Th2 activation program. Type I IL-1R ligand-binding antagonists, IL-1R antagonist and anti-type I mAb, were used to evaluate the functional significance of Th2 cell expression of two IL-1R isoforms. The addition of either IL-1R antagonist or anti-type I mAb completely inhibited the IL-1-alpha-augmented component of the proliferative response stimulated by anti-CD3 plus exogenous IL-1-alpha. Together, these studies indicate that, although Th2 clones express inducible levels of both type I and type II IL-1R isoforms, the IL-1 -induced intracellular signals involved in augmenting an anti-CD3-stimulated proliferative response are mediated solely through the type I IL-1R.