Donor APCs are required for maximal GVHD but not for GVL.
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.
Section of Medical Oncology, Yale University School of Medicine, PO Box 208032, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Catherine C
CC
Matte
Jinli
J
Liu
James
J
Cormier
Britt E
BE
Anderson
Ioanna
I
Athanasiadis
Dhanpat
D
Jain
Jennifer
J
McNiff
Warren D
WD
Shlomchik
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000637:transplantation; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D003713:Dendritic Cells / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology* / Q000502:physiology; D006652:Histological Techniques; D015466:Leukemia, Myeloid, Chronic-Phase / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000473:pathology