The role of BAFF in the Allo-immune Response

BAFF 在同种免疫反应中的作用

• 批准号: nhmrc : 427649
• 负责人: Dr Shane Grey
• 金额: $ 26.74万
• 依托单位: Garvan Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-baff-allo-immune-response/95300
• 关键词: role; BAFF; Allo; immune; Response

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.

了解控制T细胞反应的因素一直是免疫学的主要焦点。尽管如此，控制T细胞发育、稳态和功能的因素仍然不完全清楚。因此，我们一直在研究TNF家族细胞因子BAFF（TNF家族的B细胞活化因子）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细胞反应发挥促炎作用。令人惊讶的是，当我们在同种免疫应答的背景下检查BAFF对体内T细胞功能的作用时，我们发现约60%的BAFF转基因小鼠未能排斥完全错配的同种异体移植物。有趣的是，BAFF转基因小鼠表现出外周中CD4+ CD25+ Foxp3+细胞数量增加，并且这些CD25+细胞的体内消耗恢复了BAFF转基因小鼠排斥同种异体移植物的能力。我们假设BAFF在调节某些T细胞依赖性免疫应答中发挥潜在的强大抗炎作用。我们的数据表明，BAFF可以通过影响T细胞调节来调节T细胞功能。