Wang, HuiYang, YanpingWang, GuanjunWang, ShumeiYeap, BeowSykes, MeganYang, Yong-Guang2013-04-082012Wang, Hui, Yanping Yang, Guanjun Wang, Shumei Wang, Beow Yong Yeap, Megan Sykes, and Yong-Guang Yang. 2012. Donor bone marrow-derived T cells inhibit GVHD induced by donor lymphocyte infusion in established mixed allogeneic hematopoietic chimeras. PLoS ONE 7(10): e47120.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10511337Delayed administration of donor lymphocyte infusion (DLI) to established mixed chimeras has been shown to achieve anti-tumor responses without graft-vs.-host disease (GVHD). Herein we show that de novo donor BM-derived T cells that are tolerant of the recipients are important in preventing GVHD in mixed chimeras receiving delayed DLI. Mixed chimeras lacking donor BM-derived T cells developed significantly more severe GVHD than those with donor BM-derived T cells after DLI, even though both groups had comparable levels of total T cells at the time of DLI. Post-DLI depletion of donor BM-derived T cells in mixed chimeras, as late as 20 days after DLI, also provoked severe GVHD. Although both CD4 and CD8 T cells contributed to the protection, the latter were significantly more effective, suggesting that inhibition of GVHD was not mainly mediated by CD4 regulatory T cells. The lack of donor BM-derived T cells was associated with markedly increased accumulation of DLI-derived alloreactive T cells in parenchymal GVHD target tissues. Thus, donor BM-derived T cells are an important factor in determining the risk of GVHD and therefore, offer a potential therapeutic target for preventing and ameliorating GVHD in the setting of delayed DLI in established mixed chimeras.en-USBiologyImmunologyImmune CellsT CellsImmunologic SubspecialtiesTransplantationImmunopathologyMedicineClinical ImmunologyHematologyBone Marrow and Stem Cell TransplantationHematopoiesisOncologyCancer TreatmentBone Marrow TransplantationJournal Article2013-04-0810.1371/journal.pone.0047120