| First Author | Matte CC | Year | 2004 |
| Journal | Nat Med | Volume | 10 |
| Issue | 9 | Pages | 987-92 |
| PubMed ID | 15286785 | Mgi Jnum | J:92850 |
| Mgi Id | MGI:3054609 | Doi | 10.1038/nm1089 |
| Citation | Matte CC, et al. (2004) Donor APCs are required for maximal GVHD but not for GVL. Nat Med 10(9):987-92 |
| abstractText | 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. |
