The relative contribution of central and peripheral mechanisms to the generation and maintenance of allograft tolerance is of considerable interest. Here, we present new evidence that regulatory T cells (Foxp3+) maintain skin and heart allograft tolerance in mixed hematopoietic chimeric mice. Transient depletion of both donor-and recipient-derived Foxp3+ cells was necessary and sufficient to induce decisive rejection of long-accepted skin and heart allografts. In contrast, stable hematopoietic chimerism remained, and there was no detectable induction of donor-specific reactivity to hematopoietic cells. Foxp3+ cell depletion did not result in the rejection of skin grafts of only MHC-disparate donors (B6.C-H2d/bByJ), indicating that MHC antigens were not the target in the graft. We conclude that two different mechanisms of tolerance are present in mixed chimeras. Hematopoietic chimerism, resistant to Foxp3+ depletion, is probably due to deletional tolerance to MHC antigens, as supported by previous studies. In contrast, regulatory tolerance mechanisms involving Foxp3+ cells are required to control reactivity against non-MHC antigens not present on hematopoietic lineages.
|ジャーナル||American Journal of Transplantation|
|出版ステータス||Published - 2014 10月 1|
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