Opposing effects of TGF-beta 2 on the Th1 cell development of naive CD4+ T cells isolated from different mouse strains.
The development of naive dense CD4+ T cells from different mouse strains toward Th1 cells, as monitored by measuring secondary IFN-gamma production, was affected by TGF-beta 2 in a differential way. Th1 cell development of naive CD4+ T cells from strains C57Bl/6, BALB/c, and NMRI primed by immobilized anti-CD3 mAb was strongly inhibited in the presence of TGF-beta 2. Even when the Th1 cell-inducer IL-12 was added, the same effect of TGF-beta 2 was observed. In contrast, Th1 development was substantially promoted by TGF-beta 2 with T cells from C3H/He and CBA/J mice. Further analyses using CD4+ T cells from (C57Bl/6xCBA/J)F1 hybrids or DBA/1 mice showed that Th1 development was inhibited by TGF-beta 2 if the T cells were activated by anti-CD3 mAb, but it was enhanced upon costimulation with anti-CD28 mAb. Determination of primary IL-2 production revealed that T cells from (C57Bl/6xCBA/J)F1 and DBA/1 mice produced low amounts of IL-2 following stimulation by anti-CD3 mAb alone and comparatively high amounts after coactivation by anti-CD28 mAb. In the presence of TGF-beta 2, the production of IL-2 was completely suppressed if such T cells were activated solely by anti-CD3 mAb, but it was only partially inhibited after costimulation by anti-CD28 mAb. Furthermore, TGF-beta 2-promoted Th1 development of such T cells was strongly inhibited after neutralization of endogenously produced IL-2 and completely restored by the addition of human IL-2. Thus, our results indicate that the TGF-beta 2-mediated stimulation of Th1 cell development requires the presence of relatively high concentrations of IL-2. Therefore, the opposing effect of TGF-beta 2 on the Th1 cell development of naive CD4+ T cells from different mouse strains appears to be the result of the variable potency of the respective CD4+ T cells to produce IL-2 in the presence of TGF-beta 2.
Hoehn
P
P
Institute for Immunology, Johannes Gutenberg University, Mainz, Germany.
Goedert
S
S
Germann
T
T
Koelsch
S
S
Jin
S
S
Palm
N
N
Ruede
E
E
Schmitt
E
E
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D018417:Th1 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D007376:Interleukin-2; D016212:Transforming Growth Factor beta