IL-4 in combination with TGF-beta favors an alternative pathway of Th1 development independent of IL-12.
IL-4 was found to be the essential differentiation factor for Th2 cells and simultaneously to be a potent inhibitor of Th1 development that is induced by IFN-gamma and IL-12. Furthermore, it was demonstrated that TGF-beta can also inhibit Thl development. In this work, we demonstrate that polyclonal activation of Mel-14highCD4+ T cells by immobilized anti-alphabetaTCR mAb together with a mixture of IL-4 and TGF-beta can lead to the development of both Th1 and Th2 cells, depending on the concentration of these cytokines. Additional experiments revealed that Th1 induction by a combination of IL-4 and TGF-beta depends on the presence of endogenous IFN-gamma, and that this alternative Th1 development is further enhanced by IL-12, but is not dependent on this cytokine. Moreover, naive OVA323-339-specific Th cells that were stimulated by APCs and OVA323-339 peptide differentiated toward Th1 cells after priming in the presence of IL-4 in combination with TGF-beta. Hence, this finding confirmed the results obtained by polyclonal activation of naive CD4+ Th cells and implicates that this alternative Th1 development may also occur in vivo under the influence of TGF-beta and IL-4 independently of the Th1-promoting effect of IL-12.
Lingnau
K
K
Institute for Immunology, Johannes Gutenberg University, Mainz, Germany.
Hoehn
P
P
Kerdine
S
S
Koelsch
S
S
Neudoerfl
C
C
Palm
N
N
Ruede
E
E
Schmitt
E
E
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology*; D018664:Interleukin-12 / Q000494:pharmacology / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009994:Osmolar Concentration; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma