       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).

