American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
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Reduced intensity conditioning (RIC) prior to allogeneic hematopoietic cell transplantation (HCT) has shown promise in lowering the incidence of post-transplant complications including infection and graft-versus-host disease. T-cell-mediated graft rejection, however, remains a crucial factor in determining how 'mild' a level of immunosuppression can be administered. Understanding the kinetics of resistance responses as well as the role of CD4+ and CD8+ T cells underlies the development of protocols to circumvent resistance and support hematopoietic engraftment. ⋯ Host CD4+ T cells were required for optimal expansion of specific (H60) T-cell receptor (TCR) expressing host anti-donor MiHA reactive CD8+ T cells following HCT. These observations demonstrate a critical role for host CD4+ T cells in resistance against MiHA disparate HCT. This RIC HCT resistance model will be useful for the analysis of the barrier to engraftment mediated by host T cells and the development of strategies to support engraftment.