期刊
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
卷 45, 期 10, 页码 942-947出版社
ASSOC BRAS DIVULG CIENTIFICA
DOI: 10.1590/S0100-879X2012007500089
关键词
Skin graft; Tolerance; B cells; Treg; Histopathology
资金
- CNPq [30.8961/2007-2, 47.1108/2007-3, 47.4519/2004-0]
- FAPERJ [E-26/102.798/2008, E-26/110.949/2008]
- Swiss Bridge Foundation [2301500]
The participation of regulatory T (Treg) cells in B cell-induced T cell tolerance has been claimed in different models. In skin grafts, naive B cells were shown to induce graft tolerance. However, neither the contribution of Treg cells to B cell-induced skin tolerance nor their contribution to the histopathological diagnosis of graft acceptance has been addressed. Here, using male C57BL/6 naive B cells to tolerize female animals, we show that skin graft tolerance is dependent on CD25(+) Treg cell activity and independent of B cell-derived IL-10. In fact, B cells from IL-10-deficient mice were able to induce skin graft tolerance while Treg depletion of the host inhibited 100% graft survival. We questioned how Treg cell-mediated tolerance would impact on histopathology. B cell-tolerized skin grafts showed pathological scores as high as a rejected skin from naive, non-tolerized mice due to loss of skin appendages, reduced keratinization and mononuclear cell infiltrate. However, in tolerized mice, 40% of graft infiltrating CD4(+) cells were FoxP3(+) Treg cells with a high Treg:Teff (effector T cell) ratio (6:1) as compared to non-tolerized mice where Tregs comprise less than 8% of total infiltrating CD4 cells with a Treg:Teff ratio below 1:1. These results render Treg cells an obligatory target for histopathological studies on tissue rejection that may help to diagnose and predict the outcome of a transplanted organ.
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