Letter | Published:

Donor APCs are required for maximal GVHD but not for GVL

Nature Medicine volume 10, pages 987992 (2004) | Download Citation



Graft-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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We thank M. Shlomchik for discussions and reading of the manuscript. This work was supported by National Institutes of Health RO1 grants CA96943 and HL66279. W.D.S. was supported by National Institutes of Health grant K08 HL03979 and B.E.A. was supported by National Institutes of Health grant T32 AI071019-23-25.

Author information


  1. Section of Medical Oncology, Yale University School of Medicine, PO Box 208032, 333 Cedar Street, New Haven, Connecticut 06520, USA.

    • Catherine C Matte
    • , Jinli Liu
    • , Ioanna Athanasiadis
    •  & Warren D Shlomchik
  2. Department of Biochemistry and Molecular Biology, 913 Lederle Graduate Research Tower, 710 North Pleasant Street, University of Massachusetts, Amherst, Massachusetts 01003, USA.

    • James Cormier
  3. Department of Laboratory Medicine, PO Box 208035; Yale University School of Medicine, 333 Cedar St., New Haven, Connecticut 06520, USA.

    • Britt E Anderson
  4. Department of Pathology, PO Box 208023; Yale University School of Medicine, 333 Cedar St., New Haven, Connecticut 06520, USA.

    • Dhanpat Jain
  5. Department of Dermatology, PO Box 208059; Yale University School of Medicine, 333 Cedar St., New Haven, Connecticut 06520, USA.

    • Jennifer McNiff
  6. Section of Immunobiology, PO Box 208035; Yale University School of Medicine, 333 Cedar St., New Haven, Connecticut 06520, USA.

    • Warren D Shlomchik


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The authors declare no competing financial interests.

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Correspondence to Warren D Shlomchik.

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