Evidence of positive cross-regulation on Th1 by Th2 and antigen-presenting cells: effects on Th1 induced by IL-4 and IL-12.
The response of Th cells to cytokines is normally strictly regulated, such that following antigenic stimulation, Th cells respond for only a short period of time, after which they become refractory to cytokine-mediated effects. IL-12, a costimulator of Th1 having no proliferation-inducing capacity of its own, allows Th1 clones and lines to respond to IL-4 when they would otherwise be unable to respond to this cytokine. Cells that have proliferated in response to IL-4 plus IL-12 are fully able to be subsequently activated by specific Ag and APC. Additionally, the response to IL-4 of Th1 effector cells derived from normal murine spleen is enhanced significantly by IL-12. Furthermore, in the presence of IL-12, stimulated Th2 can induce proliferation of Th1 via IL-4 production, in a dual chamber culture system. We hypothesize that the effects of IL-4 and IL-12 represent a novel, positive cross-regulatory pathway that acts on Th1, and is mediated by Th2 (the IL-4 source) and APC (the IL-12 source). We propose this as a way for a Th2 immune response to positively influence an ongoing or waning Th1 response.
Oriss
T B
TB
University of Pittsburgh Cancer Institute, Department of Medicine, PA 15213, USA.
McCarthy
S A
SA
Campana
M A
MA
Morel
P A
PA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D002469:Cell Separation; D002478:Cells, Cultured; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D018664:Interleukin-12 / Q000494:pharmacology / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology / Q000502:physiology*; D007399:Interphase / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*