Nature Medicine
10, 987 - 992 (2004)
Published online: 1 August 2004; | doi:10.1038/nm1089
Donor APCs are required for maximal GVHD but not for GVLCatherine C Matte1, Jinli Liu1, James Cormier2, Britt E Anderson3, Ioanna Athanasiadis1, Dhanpat Jain4, Jennifer McNiff5
& Warren D Shlomchik1, 61
Section of Medical Oncology, Yale University School of Medicine, PO Box 208032, 333 Cedar Street, New Haven, Connecticut 06520, USA. 2
Department of Biochemistry and Molecular Biology, 913 Lederle Graduate Research Tower, 710 North Pleasant Street, University of Massachusetts, Amherst, Massachusetts 01003, USA. 3
Department of Laboratory Medicine, PO Box 208035; Yale University School of Medicine, 333 Cedar St., New Haven, Connecticut 06520, USA. 4
Department of Pathology, PO Box 208023; Yale University School of Medicine, 333 Cedar St., New Haven, Connecticut 06520, USA. 5
Department of Dermatology, PO Box 208059; Yale University School of Medicine, 333 Cedar St., New Haven, Connecticut 06520, USA. 6
Section of Immunobiology, PO Box 208035; Yale University School of Medicine, 333 Cedar St., New Haven, Connecticut 06520, USA.
Correspondence should be addressed to Warren D Shlomchik warren.shlomchik@yale.eduGraft-versus-host disease (GVHD) is a major source of morbidity in allogenic stem cell transplantation1. 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)2. 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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