Donor APCs are required for maximal GVHD but not for GVL
CC Matte, J Liu, J Cormier, BE Anderson… - Nature medicine, 2004 - nature.com
Nature medicine, 2004•nature.com
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 …
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 …
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.
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