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* Division of Immunology and Rheumatology, Department of Medicine, and
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305
Allogeneic bone marrow transplantation is a curative treatment for leukemia and lymphoma, but graft-vs-host disease (GVHD) remains a major complication. Using a GVHD protective nonmyeloablative conditioning regimen of total lymphoid irradiation and antithymocyte serum (TLI/ATS) in mice that has been recently adapted to clinical studies, we show that regulatory host NKT cells prevent the expansion and tissue inflammation induced by donor T cells, but allow retention of the killing activity of donor T cells against the BCL1 B cell lymphoma. Whereas wild-type hosts given transplants from wild-type donors were protected against progressive tumor growth and lethal GVHD, NKT cell-deficient CD1d–/– and J
-18–/– host mice given wild-type transplants cleared the tumor cells but died of GVHD. In contrast, wild-type hosts given transplants from CD8–/– or perforin–/– donors had progressive tumor growth without GVHD. Injection of host-type NKT cells into J-18–/– host mice conditioned with TLI/ATS markedly reduced the early expansion and colon injury induced by donor T cells. In conclusion, after TLI/ATS host conditioning and allogeneic bone marrow transplantation, host NKT cells can separate the proinflammatory and tumor cytolytic functions of donor T cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grants P01 CA-49605, P01 HL-57443, R01 HL-58250, and R01 AI-37683 from the National Institutes of Health.
2 Address correspondence and reprint requests to Dr. Samuel Strober, Department of Medicine, Division of Immunology and Rheumatology, Center for Clinical Sciences Research Building, Room 2215-C, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5166. E-mail address: sstrober{at}stanford.edu
3 Abbreviations used in this paper: GVHD, graft-vs-host disease; TLI, total lymphoid irradiation; ATG, antithymocyte globulin; ATS, antithymocyte serum; BCL1, B cell lymphoma; -GalCer, -galactosyl ceramide; DAPI, 4',6'-diamidino-2-phenylindole; TBI, total body irradiation; MLN, mesenteric lymph node.
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