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Donor APCs are required for maximal GVHD but not for GVL

Nature Medicine volume 10, pages 987–992 (2004)Cite this article

Abstract

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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Figure 1: Recipients of B2m−/− bone marrow (BM) develop less GVHD.
Figure 2: Splenic DCs in mice with GVHD were donor-derived.
Figure 3: MHC II+ cells in skin and bowel are donor-derived.
Figure 4: Donor APCs are not required for CD8-mediated GVL.

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Acknowledgements

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.

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Authors and Affiliations

  1. Section of Medical Oncology, Yale University School of Medicine, PO Box 208032, 333 Cedar Street, New Haven, 06520, Connecticut, 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, 01003, Massachusetts, USA

    James Cormier

  3. Department of Laboratory Medicine, PO Box 208035

    Britt E Anderson

  4. Yale University School of Medicine, 333 Cedar St., New Haven, 06520, Connecticut, USA

    Britt E Anderson

  5. Department of Pathology, PO Box 208023

    Dhanpat Jain

  6. Yale University School of Medicine, 333 Cedar St., New Haven, 06520, Connecticut, USA

    Dhanpat Jain

  7. Department of Dermatology, PO Box 208059

    Jennifer McNiff

  8. Yale University School of Medicine, 333 Cedar St., New Haven, 06520, Connecticut, USA

    Jennifer McNiff

  9. Section of Immunobiology, PO Box 208035

    Warren D Shlomchik

  10. Yale University School of Medicine, 333 Cedar St., New Haven, 06520, Connecticut, USA

    Warren D Shlomchik

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  1. Catherine C Matte
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Correspondence to Warren D Shlomchik.

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Matte, C., Liu, J., Cormier, J. et al. Donor APCs are required for maximal GVHD but not for GVL. Nat Med 10, 987–992 (2004). https://doi.org/10.1038/nm1089

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