Function of the Bone Morphogenetic Protein in Immune System

激活素是转化生长因子-b（TGF-β）超家族的成员，是一种多能生长和分化因子。在许多生物系统中，激活素与TGF-β具有重叠的生物活性，部分原因是激活素和TGF-β在信号转导中使用相同的蛋白质（Smad2和/或Smad3）。激活素在免疫系统中的表达和功能尚未完全表征，这与对TGF-β功能的广泛了解形成了对比。抑制T细胞增殖分化为效应细胞，诱导T细胞凋亡。我们研究了激活素A在CD4^+辅助性T细胞中的调控表达。我们的研究结果表明，激活素A是由CD4^+T细胞响应其激活而产生的。近年来，CD4+CD25+调节性T细胞作为一种独特的抑制性T细胞群体出现，它们产生高水平的TGF-β，参与维持外周免疫耐受。我们确定激活素A是否在CD4^+CD25^+T细胞中产生，并作为T细胞功能的抑制因子。CD4^+CD25^+调节性T细胞即使受到抗cd3和抗cd28单克隆抗体刺激，也未检测到激活素的表达，尽管TGF-b1高表达。在培养物中加入激活素A、卵泡抑素或抗激活素单抗对CD4^+CD25^+调节性T细胞体外抑制T细胞增殖几乎没有影响。相比之下，TGF-β1有效抑制t细胞增殖，但激活素A不有效，且呈剂量依赖性。因此，至少在CD4^+ T细胞的增殖上，激活素的功能不同于TGF-β。

Activins, members of the transforming growth factor-b(TGF-β) superfamily, are pluripotent growth and differentiation factors. In many biological systems, activins have overlapping biological activities with TGF-β partly due to the fact that activins and TGF-bs utilize the same proteins (Smad2 and/or Smad3) in signal transduction. The expression and function of activin in the immune system are not yet fully characterized, in contrast to the extensive knowledge of TGF-β's functions. It inhibits the proliferation and differentiation into effector cells, and induces the apoptosis in T cells. We investigated the regulatory expression of activin A in CD4^+ helper T cells. Our results revealed that activin A is produced by CD4^+T cells in response to their activation. In recent years, CD4+CD25+ regulatory T cells have emerged as a unique population of suppressor T cells that produce high levels of TGF-β that is involved in maintaining peripheral immune tolerance. We determined if activin A is produced in CD4^+CD25^+T cells and acts as a suppressor of T cell functions. Activin expression was not detected in CD4^+CD25^+ regulatory T cells even when they were stimulated with anti-CD3 and anti-CD28 mAbs, although TGF-b1 was highly expressed. Addition of activin A, follistatin or anti-activin mAb to the culture barely affected the in vitro suppression of T cell proliferation by CD4^+CD25^+ regulatory T cells. In contrast, TGF-β1 but not activin A efficientiy inhibited T-cell proliferation in a dose-dependent manner. Thus, the function ofactivin is distinct from that of TGF-β at least on the proliferation of CD4^+ T cells.