Autoantibody production in lpr/lpr gld/gld mice reflects accumulation of CD4(+) effector cells that are resistant to regulatory T cell activity

作者：Hondowicz Brian D; Fields Michele L; Nish Simone A; Larkin Joseph III; Caton Andrew J; Erikson Jan^*

来源：Journal of Autoimmunity, 2008, 31(2): 98-109.

DOI：10.1016/j.jaut.2008.04.022

• Autoantibody
• Fas/FasL
• IFN-gamma
• T regulatory

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.

• 出版日期2008-9