Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming.
Naive CD4+ T cells produce interleukin 2 (IL-2) but little IL-4 or interferon gamma (IFN-gamma). In vitro, they develop into IL-4 or IFN-gamma producers depending on the conditions of the priming culture. Using T-cell receptor transgenic CD4+ T cells, the role of IL-12 and IL-4 in antigen-specific priming was examined. IL-12 substantially enhanced the ability of naive CD4+ T cells to develop into cells that produced IFN-gamma upon restimulation. However, it was not essential since anti-IL-12 antibodies failed to block the priming for IFN-gamma observed in the absence of exogenous IL-12. When both IL-12 and IL-4 were present in the priming culture, IL-12 did not inhibit priming for IL-4 production. In contrast, IL-4 diminished but did not abolish priming for IFN-gamma production. In an accessory cell-independent priming system, IL-12 strikingly augmented priming for IFN-gamma production, indicating that it acts directly on T cells. IFN-gamma itself did not enhance priming for IFN-gamma production in either accessory cell-dependent or independent systems. In an accessory cell-dependent system, the IL-12-mediated enhancement was not blocked by adding neutralizing anti-IFN-gamma monoclonal antibody. However, in an accessory cell-independent system, anti-IFN-gamma antibody did inhibit priming for IFN-gamma production leaving open a role for IFN-gamma in the priming process. These data indicate that IL-12 has a major effect on the inductive phase of T-cell priming by enhancing commitment to IFN-gamma production and thus can profoundly influence the state of immunity that develops.
Seder
R A
RA
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Gazzinelli
R
R
Sher
A
A
Paul
W E
WE
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D005260:Female; D006133:Growth Substances / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018664:Interleukin-12; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D007700:Kinetics; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*
D015704:CD4 Antigens; D006133:Growth Substances; D007376:Interleukin-2; D007378:Interleukins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma