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Graft-Versus-Host Disease

Adoptive transfer of small numbers of DX5+ cells alleviates graft-versus-host disease in a murine model of semiallogeneic bone marrow transplantation: a potential role for NKT lymphocytes

Bone Marrow Transplantation volume 35, pages 191–197 (2005)Cite this article

Abstract

Summary:

Natural killer T (NKT) lymphocyte cells are a subset of regulatory lymphocytes with important immunemodulatory effects. Our aim was to evaluate the effect of transplantation of NKT lymphocytes on graft versus host disease (GVHD) in a murine model of semiallogeneic BMT. GVHD was generated by infusion of 2 × 107 splenocytes from C57BL/6 donor mice into irradiated (C57BL/6 × Balb/c)F1 recipient mice. Adoptive transfer of increasing numbers of DX5+ cells was performed. Recipient mice were followed for histological parameters of GVHD-associated liver, bowel, and cutaneous injury. Intrahepatic and intrasplenic lymphocytes were isolated and analyzed by FACS for CD4+ and CD8+ subpopulations. It was seen that adoptive transfer of 4.5 × 106 DX5+ cells significantly alleviated GVHD-related hepatic, bowel, and cutaneous injury, and improved survival (85% survival on day 28). In contrast, depletion of DX5+ cells led to severe GVHD-associated multiorgan injury and 100% mortality. A direct correlation with the number of transplanted DX5+ cells was noted (maximal effect with transplantation of 4.5 × 106 DX5+ cells). Tolerance induction was associated with an increased peripheral CD4/CD8 ratio, intrahepatic trapping of CD8 lymphocytes and a shift towards a Th2-type cytokine profile, manifested by decreased IL-12/IL10, IL-12/IL-4, IFNγ/IL-10, and IFNγ/IL-4 ratios. Transplantation of DX5+ cells holds promise as a novel therapeutic measure for GVHD.

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Acknowledgements

This work was supported in part by the following grants: Israel Cancer Research Fund (to AN); grants from ENZO Biochem Inc., NY and the Roaman-Epstein Liver Research Foundation (to YI).

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Author notes

  1. M Margalit and Y Ilan: First two authors contributed equally.

Authors and Affiliations

  1. Liver Unit, Department of Medicine, Hadassah Hebrew University Medical Center, Jerusalem

    M Margalit, Y Ilan, R Safadi & R Alper

  2. Department of Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel

    M Ohana & A Nagler

  3. Department of Pathology, Hadassah Hebrew University Medical Center, Jerusalem

    Y Sherman & V Doviner

  4. ENZO Biochem Inc., NY, USA

    E Rabbani & D Engelhardt

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  1. M Margalit
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Correspondence to Y Ilan.

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Margalit, M., Ilan, Y., Ohana, M. et al. Adoptive transfer of small numbers of DX5+ cells alleviates graft-versus-host disease in a murine model of semiallogeneic bone marrow transplantation: a potential role for NKT lymphocytes. Bone Marrow Transplant 35, 191–197 (2005). https://doi.org/10.1038/sj.bmt.1704719

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