Crossregulation between T helper cell (Th)1 and Th2: inhibition of Th2 proliferation by IFN-gamma involves interference with IL-1.
The Th1-derived cytokine IFN-gamma inhibits the proliferation of Th2 lymphocytes, but the mechanism of inhibition is not known. Under certain disease conditions, an established Th2-mediated immune response is undesirable and a Th1-mediated response is beneficial. However, established Th2 cells appear to be phenotypically stable. Thus, learning more about cytokine-mediated regulation of established Th2 cells is important if deleterious immune responses are to be altered. We studied the effects of IFN-gamma on a panel of recently derived Th2 lines and clones, as well as a previously established Th2 clone, 13.26. Inhibition by IFN-gamma was observed only when there was a concomitant response to IL-1, a known costimulator of Th2. Clone 13.26 was particularly sensitive to both IL-1 and IFN-gamma, so it was studied in greater detail. We examined cytokine responses using stimulation by anti-TCR mAb-coated plates, or Ag presented by APC populations that do or do not produce IL-1. All IL-1-mediated proliferative responses of 13.26 were inhibited by IFN-gamma, whereas IL-1-independent (IL-4-associated) responses were unaffected. Our data suggest that IFN-gamma inhibits Th2 proliferation through an IL-1-dependent mechanism, and furthermore, that the costimulatory pathways used by APCs may be critical for subsequent Th cell responses to cytokines.
Oriss
T B
TB
University of Pittsburgh Cancer Institute and Department of Medicine, PA 15213, USA.
McCarthy
S A
SA
Morel
B F
BF
Campana
M A
MA
Morel
P A
PA
D000818:Animals; D002450:Cell Communication; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D007375:Interleukin-1 / Q000276:immunology*; D051379:Mice; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
D007375:Interleukin-1; D007371:Interferon-gamma