Comparison of the immunosuppressive properties of milk growth factor and transforming growth factors beta 1 and beta 2.
Comparison of the immunosuppressive properties of milk growth factor and transforming growth factors beta 1 and beta 2.
复制标题
乳生长因子与转化生长因子β1和β2的免疫抑制特性比较。
作者：
M. Stoeck;C. Ruegg;S. Miescher;S. Carrel;D. Cox;V. V. von Fliedner;S. Alkan
研究了新分离的与转化生长因子β 2 n端同源的牛乳生长因子（MGF）与猪转化生长因子β 1和β 2 （ptgf - β 1和- β 2）对人T淋巴细胞活化的影响。用PHA、抗cd3 + phorol -12,13-dibutyrate （PDBu）或离子霉素+ PDBu的组合刺激新鲜分离的人PBMC。MGF、ptgf - β 1和ptgf - β 2以剂量依赖性的方式减少了丝裂原诱导的[3H]胸腺嘧啶掺入30%至75%。在1 ng/ml （40 pM）时达到最大抑制程度，并且不能通过将转化生长因子浓度增加10倍来增强。MGF在pM浓度下对新鲜T细胞的破伤风抗原类毒素刺激也被抑制（85%），纯化蛋白衍生物特异性人T细胞克隆的增殖也被抑制。采用Fura-2法研究MGF和ptgf - β 1对抗cd3介导的细胞内Ca2+ (Cai2+)升高的影响。MGF和ptgf - β 1均不能抑制抗cd3抗体浓度诱导的Cai2+的增加。为了确定tgf - β是否优先抑制人T细胞的CD4+或CD8+亚群，使用了一种限制稀释分析系统，该系统允许每个T细胞增殖。浓度为5ng /ml的ptgf - β 1在相似程度上降低了CD4+和CD8+亚群的增殖T细胞前体的频率。此外，MGF、ptgf - β 1和ptgf - β 2还能将IL-2介导的[3H]胸腺嘧啶掺入人PBL Con A原细胞和il -4介导的[3H]胸腺嘧啶掺入与PDBu共刺激的纯化T淋巴细胞减少70%。综上所述，牛MGF对Ag、有丝分裂原或白细胞介素刺激的人T细胞具有抑制作用，其抑制程度与ptgf - β 1或- β 2相似（或相同）。
The effects of the newly isolated bovine milk growth factor (MGF) which shows N-terminal homology to transforming growth factor beta 2 were compared with the effects of porcine transforming growth factor beta 1 and beta 2 (pTGF-beta 1 and -beta 2) on human T lymphocyte activation. Freshly isolated human PBMC were stimulated with either PHA, anti-CD3 + phorbol-12,13-dibutyrate (PDBu), or with a combination of ionomycin + PDBu. MGF, pTGF-beta 1, and pTGF-beta 2 decreased mitogen-induced [3H]thymidine incorporation by 30 to 75% in a dose-dependent manner. The maximum degree of inhibition was obtained at 1 ng/ml (40 pM) and could not be increased by increasing the concentration of teh transforming growth factor 10-fold. Stimulation of fresh T cells with the recall Ag tetanus toxoid was also inhibited (85%) by MGF at pM concentrations as was the proliferation of a human T cell clone specific for purified protein derivative. The effects of MGF and pTGF-beta 1 on anti-CD3-mediated increase of intracellular Ca2+ (Cai2+) was investigated by using the Fura-2 method. Neither MGF nor pTGF-beta 1 inhibited this increase in Cai2+ induced by a mitogenic concentration of anti-CD3 antibody. In order to determine whether TGF-beta preferentially inhibited the CD4+ or CD8+ subpopulation of human T cells, a limiting dilution analysis system, which allows every T cell to proliferate, was used. pTGF-beta 1 at a concentration of 5 ng/ml decreased the frequency of proliferating T cell precursors of both the CD4+ and CD8+ subsets to a similar extent. Furthermore, MGF, pTGF-beta 1, and pTGF-beta 2 also decreased IL-2 mediated [3H]thymidine incorporation into human PBL Con A blasts and the IL-4-mediated [3H]thymidine incorporation of purified T lymphocytes costimulated with PDBu by 70%. In conclusion, bovine MGF exerts suppressive effects on human T cells stimulated with Ag, mitogens, or interleukins, and the degree of T cell suppression is similar (or identical) to those of pTGF-beta 1 or -beta 2.