The role of BAFF in the Allo-immune Response

了解控制T细胞反应的因素一直是免疫学的主要焦点。尽管做出了这些努力，但控制T细胞发育、动态平衡和功能的因素仍然不完全清楚。因此，我们一直在研究肿瘤坏死因子家族细胞因子BAFF(肿瘤坏死因子家族的B细胞激活因子)与T细胞行为和功能的关系。虽然BAFF最初被描述为对B细胞的发育和成熟至关重要，但许多证据表明，BAFF在T细胞生物学中可能是重要的。目前的研究表明，BAFF对T细胞反应具有促炎作用。令人惊讶的是，当我们在同种异体免疫反应的背景下检查BAFF对体内T细胞功能的作用时，我们发现~60%的BAFF转基因小鼠未能排斥完全不相合的同种异体移植。有趣的是，BAFF转基因小鼠外周血中的CD4+CD25+Foxp3+细胞数量增加，体内这些CD25+细胞的耗尽恢复了BAFF转基因小鼠排斥同种异体移植的能力。我们推测，BAFF在调节某些T细胞依赖的免疫反应方面具有潜在的强大抗炎作用。我们的数据提示，BAFF可以通过影响T细胞调节来调节T细胞功能。

Understanding the factors that control T cell responses has been a major focus of immunology. Despite this effort the factors that control T cell development, homeostasis and function are still only incompletely understood. Accordingly we have been studying the TNF-family cytokine BAFF (B cell activation factor of the TNF-family) in relation to T cell behaviour and function. Though BAFF was first described as being critical for B cell development and maturation, a number of lines of evidence indicate that BAFF may be important in T cell biology. Current studies suggest that BAFF exerts a pro-inflammatory effect upon T cell responses. Surprisingly then, when we examined the role of BAFF upon T cell function in vivo in the context of the allo-immune response, we found that ~60% of BAFF transgenic mice failed to reject a fully-mismatched allograft. Intriguingly, BAFF transgenic mice exhibited an increased number of CD4+ CD25+ Foxp3+ cells in the periphery and in vivo depletion of these CD25+ cells restored the ability of BAFF transgenic mice to reject an allograft. We hypothesize that BAFF plays a potentially powerful anti-inflammatory role in regulating certain T cell dependent immune responses. Our data suggests that BAFF can modulate T cell function by effecting T cell regulation.