"Pruning" of alloreactive CD4+ T cells using 5- (and 6-)carboxyfluorescein diacetate succinimidyl ester prolongs skin allograft survival

摘要: Removal of alloreactive cells by either thymic deletion or deletion/anergy in the periphery is regarded as crucial to development tolerance. Dyes, such CFSE, that allow monitoring cell division suggest vitro proliferation could be a used way "pruning" while retaining normal immune repertoire with retention memory previously encountered pathogens. This would overcome problems occurring result therapies use massive depletion T acceptance organ transplants bone marrow grafts. We therefore skin graft model CD4-mediated rejection across major H-2 mismatch (C57BL/6 (H-2(b)) BALB/c (H-2(d)) mice) evaluate whether nondividing CD4(+) derived from mixed lymphocyte culture exhibit tolerance initial stimulator strain. demonstrate selective removal dividing resulted marked specific prolongation allogeneic survival, and retained broad TCR ability maintain memory. novel depleting may serve useful strategy combination other mechanisms achieve transplant