Hondowicz Brian D, Fields Michele L, Nish Simone A, Larkin Joseph, Caton Andrew J, Erikson Jan
The Wistar Institute, Room 276, 3601 Spruce Street, Philadelphia, PA 19104, USA.
J Autoimmun. 2008 Sep;31(2):98-109. doi: 10.1016/j.jaut.2008.04.022. Epub 2008 Jun 9.
In Fas/FasL-deficient mice anti-chromatin Ab production is T cell dependent and is not apparent until after 10 weeks of age. Early control of anti-chromatin antibodies may be due to the counterbalancing influence of Treg cells. Here we show that Treg cells block lpr/lpr gld/gld Th cells from providing help to anti-chromatin B cells in an in vivo transfer system. Interestingly, the percentage and absolute numbers of Foxp3+ Treg cells is elevated in BALB/c-lpr/lpr gld/gld mice and increases with age compared to BALB/c mice. The majority of Foxp3 expression is found in the B220- CD4+ T cell population, and Foxp3-expressing cells are localized in the splenic PALS (periarteriolar lymphocyte sheath). Strikingly, although the lack of functional Fas/FasL does not affect the ability of Treg cells to block Th cell proliferation, Treg cells can block the IFN-gamma differentiation of Th cells from BALB/c or young BALB-lpr/lpr gld/gld mice but not of pre-existing Th1 cells from older BALB/c-lpr/lpr gld/gld mice. Thus, we suggest autoantibody production is not caused by the lack of Treg cells but by a defect in activation-induced cell death that leads to the accumulation of T effector cells that are resistant to regulatory T cell activity.
在Fas/FasL缺陷小鼠中，抗染色质抗体的产生依赖于T细胞，且直到10周龄后才会明显出现。抗染色质抗体的早期控制可能归因于调节性T细胞的平衡影响。在此我们表明，在体内转移系统中，调节性T细胞可阻止lpr/lpr gld/gld T细胞为抗染色质B细胞提供帮助。有趣的是，与BALB/c小鼠相比，BALB/c-lpr/lpr gld/gld小鼠中Foxp3+调节性T细胞的百分比和绝对数量有所升高，且随年龄增长而增加。大多数Foxp3表达见于B220-CD4+ T细胞群体，且表达Foxp3的细胞定位于脾脏的动脉周围淋巴细胞鞘（PALS）。引人注目的是，尽管功能性Fas/FasL的缺失并不影响调节性T细胞阻止T细胞增殖的能力，但调节性T细胞可阻止来自BALB/c或年轻BALB-lpr/lpr gld/gld小鼠的T细胞分化为IFN-γ，但不能阻止来自老年BALB/c-lpr/lpr gld/gld小鼠的预先存在的Th1细胞分化。因此，我们认为自身抗体的产生不是由调节性T细胞的缺乏引起的，而是由激活诱导的细胞死亡缺陷导致对调节性T细胞活性有抗性的T效应细胞积累所致。
