Murine T helper cell-2 lymphocytes express type I and type II IL-1 receptors, but only the type I receptor mediates costimulatory activity.
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.
Department of Immunology, Mayo Clinic, Rochester, MN 55905.
D J
DJ
McKean
R P
RP
Podzorski
M P
MP
Bell
A E
AE
Nilson
C J
CJ
Huntoon
J
J
Slack
S K
SK
Dower
J
J
Sims
D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000032:analysis; D017472:Receptors, Interleukin-1 / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000737:chemistry* / Q000276:immunology
D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1