Hoehn P, Goedert S, Germann T, Koelsch S, Jin S, Palm N, Ruede E, Schmitt E
Institute for Immunology, Johannes Gutenberg University, Mainz, Germany.
J Immunol. 1995 Oct 15;155(8):3788-93.
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.
通过检测二次干扰素-γ的产生来监测，不同小鼠品系的初始密集CD4+ T细胞向Th1细胞的分化受到转化生长因子-β2（TGF-β2）的不同影响。在TGF-β2存在的情况下，由固定化抗CD3单克隆抗体启动的C57Bl/6、BALB/c和NMRI品系的初始CD4+ T细胞向Th1细胞的分化受到强烈抑制。即使添加了Th1细胞诱导剂白细胞介素-12（IL-12），也观察到TGF-β2的相同作用。相反，TGF-β2可显著促进C3H/He和CBA/J小鼠的T细胞向Th1细胞的分化。使用（C57Bl/6xCBA/J）F1杂交种或DBA/1小鼠的CD4+ T细胞进行的进一步分析表明，如果T细胞被抗CD3单克隆抗体激活，TGF-β2会抑制Th1细胞的分化，但在用抗CD28单克隆抗体共刺激时，Th1细胞的分化会增强。对初始白细胞介素-2产生的测定表明，（C57Bl/6xCBA/J）F1和DBA/1小鼠的T细胞在仅由抗CD3单克隆抗体刺激后产生少量白细胞介素-在抗CD28单克隆抗体共激活后产生相对大量的白细胞介素-2。在TGF-β2存在的情况下，如果此类T细胞仅由抗CD3单克隆抗体激活，白细胞介素-2的产生会被完全抑制，但在抗CD28单克隆抗体共刺激后只会被部分抑制。此外，在中和内源性产生的白细胞介素-2后，TGF-β2促进的此类T细胞向Th1细胞的分化受到强烈抑制，并通过添加人白细胞介素-2完全恢复。因此，我们的结果表明，TGF-β2介导的对Th1细胞分化的刺激需要存在相对高浓度的白细胞介素-2。因此，TGF-β2对不同小鼠品系初始CD4+ T细胞向Th1细胞分化的相反作用似乎是各自CD4+ T细胞在TGF-β2存在下产生白细胞介素-2的能力不同的结果。
