Donor APCs are required for maximal GVHD but not for GVL |
| |
Authors: | Matte Catherine C Liu Jinli Cormier James Anderson Britt E Athanasiadis Ioanna Jain Dhanpat McNiff Jennifer Shlomchik Warren D |
| |
Institution: | Section of Medical Oncology, Yale University School of Medicine, PO Box 208032, 333 Cedar Street, New Haven, Connecticut 06520, USA. |
| |
Abstract: | Graft-versus-host disease (GVHD) is a major source of morbidity in allogenic stem cell transplantation. We previously showed that recipient antigen-presenting cells (APCs) are required for CD8-dependent GVHD in a mouse model across only minor histocompatibility antigens (minor H antigens). However, these studies did not address the function of donor-derived APCs after GVHD is initiated. Here we show that GVHD develops in recipients of donor major histocompatibility complex class I-deficient (MHC I(-)) bone marrow. Thus, after initial priming, CD8 cells caused GVHD without a further requirement for hematopoietic APCs, indicating that host APCs are necessary and sufficient for GHVD. Nonetheless, GVHD was less severe in recipients of MHC I(-) bone marrow. Therefore, once initiated, GVHD is intensified by donor-derived cells, most probably donor APCs cross-priming alloreactive CD8 cells. Nevertheless, donor APCs were not required for CD8-mediated graft-versus-leukemia (GVL) against a mouse model of chronic-phase chronic myelogenous leukemia. These studies identify donor APCs as a new target for treating GVHD, which may preserve GVL. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|