Document 0405 DOCN M9610405 TI Opposing effects of TGF-beta 2 on the Th1 cell development of naive CD4+ T cells isolated from different mouse strains. DT 9601 AU Hoehn P; Goedert S; Germann T; Koelsch S; Jin S; Palm N; Ruede E; Schmitt E; Institute for Immunology, Johannes Gutenberg University, Mainz,; Germany. SO J Immunol. 1995 Oct 15;155(8):3788-93. Unique Identifier : AIDSLINE MED/96003416 AB 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. DE Animal Cell Differentiation/IMMUNOLOGY Cell Separation Cells, Cultured Comparative Study CD4-Positive T-Lymphocytes/*IMMUNOLOGY Female Human Interleukin-2/BIOSYNTHESIS/METABOLISM/PHYSIOLOGY Lymphocyte Transformation Male Mice Mice, Inbred BALB C Mice, Inbred CBA Mice, Inbred C3H Mice, Inbred C57BL Mice, Inbred DBA Support, Non-U.S. Gov't Th1 Cells/*IMMUNOLOGY Transforming Growth Factor beta/*PHYSIOLOGY JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).