Donor APCs are required for maximal GVHD but not for GVL

Nat Med. 2004 Sep;10(9):987-92. doi: 10.1038/nm1089. Epub 2004 Aug 1.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / transplantation
  • Bone Marrow Transplantation / adverse effects*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / transplantation
  • Dendritic Cells / immunology
  • Fluorescent Antibody Technique
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / immunology
  • Graft vs Leukemia Effect / immunology*
  • Graft vs Leukemia Effect / physiology
  • Histological Techniques
  • Leukemia, Myeloid, Chronic-Phase / immunology
  • Mice
  • Mice, Inbred C3H
  • Spleen / pathology