Mellanby Richard J, Thomas David, Phillips Jenny M, Cooke Anne
Immunology Division, Department of Pathology, University of Cambridge, Cambridge, UK.
Immunology. 2007 May;121(1):15-28. doi: 10.1111/j.1365-2567.2007.02546.x.
The role of regulatory T cells (Tregs) in maintaining self tolerance has been intensively researched and there is a growing consensus that a decline in Treg function is an important step towards the development of autoimmune diseases, including diabetes. Although we show here that CD25+ cells delay diabetes onset in non-obese diabetic (NOD) mice, we found, in contrast to previous reports, neither an age-related decline nor a decline following onset of diabetes in the frequency of CD4+ CD25+ Foxp3+ regulatory T cells. Furthermore, we demonstrate that CD4+ CD25+ cells from both the spleen and pancreatic draining lymph nodes of diabetic and non-diabetic NOD mice are able to suppress the proliferation of CD4+ CD25- cells to a similar extent in vitro. We also found that pretreatment of NOD mice with anti-CD25 antibody allowed T cells with a known reactivity to islet antigen to proliferate more in the pancreatic draining lymph nodes of NOD mice, regardless of age. In addition, we demonstrated that onset of diabetes in NOD.scid mice is faster when recipients are co-administered splenocytes from diabetic NOD donors and anti-CD25. Finally, we found that although diabetic CD4+ CD25+ T cells are not as suppressive in cotransfers with effectors into NOD.scid recipients, this may not indicate a decline in Treg function in diabetic mice because over 10% of CD4+ CD25+ T cells are non-Foxp3 and the phenotype of the CD25- contaminating population significantly differs in non-diabetic and diabetic mice. This work questions whether onset of diabetes in NOD mice is associated with a decline in Treg function.
调节性T细胞（Tregs）在维持自身耐受性方面的作用已得到深入研究，并且越来越多的人达成共识，即Treg功能下降是包括糖尿病在内的自身免疫性疾病发展的重要一步。尽管我们在此表明CD25 +细胞可延缓非肥胖糖尿病（NOD）小鼠的糖尿病发病，但与先前的报道相反，我们发现CD4 + CD25 + Foxp3 +调节性T细胞的频率既没有与年龄相关的下降，也没有在糖尿病发病后下降。此外，我们证明，来自糖尿病和非糖尿病NOD小鼠的脾脏和胰腺引流淋巴结的CD4 + CD25 +细胞在体外能够以相似的程度抑制CD4 + CD25-细胞的增殖。我们还发现，用抗CD25抗体预处理NOD小鼠可使对胰岛抗原有已知反应性的T细胞在NOD小鼠的胰腺引流淋巴结中增殖更多，而与年龄无关。此外，我们证明，当受体同时接受来自糖尿病NOD供体的脾细胞和抗CD25时，NOD.scid小鼠的糖尿病发病更快。最后，我们发现，尽管糖尿病CD4 + CD25 + T细胞在与效应细胞共转移到NOD.scid受体中时的抑制作用不如前者，但这可能并不表明糖尿病小鼠中Treg功能下降，因为超过10％的CD4 + CD25 + T细胞是非Foxp3细胞，并且CD25-污染群体的表型在非糖尿病和糖尿病小鼠中存在显著差异。这项工作质疑NOD小鼠的糖尿病发病是否与Treg功能下降有关。
