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Graft Versus Host Disease

Decreased graft-versus-host disease after haplotype mismatched bone marrow allografts in miniature swine following interleukin-2 treatment

Abstract

Graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation after transplants between HLA-mismatched donor/recipient pairs. In mice, giving IL-2 post transplant decreases GVHD in this setting. We studied high-dose IL-2 therapy in pigs. Transplants were carried out after conditioning with fractionated total body radiation and cyclophosphamide. Fourteen pigs received a fully mismatched bone marrow transplant (six with IL-2; eight without IL-2), and six received a single haplotype class II mismatched transplant (three with IL-2; three without IL-2). GVHD was evaluated by skin histology. All fully mismatched recipients had severe GVHD (grade 2–3) and died within 13 to 51 days whether or not they received IL-2. Pigs receiving a one haplotype class II mismatched transplant without IL-2 developed severe skin GVHD lasting for 8–45 days; all died within 57 days. Similar pigs receiving IL-2 post transplant had no or only mild skin GVHD for less than 15 days; two are long-term survivors. Bone Marrow Transplantation (2000) 25, 47–52.

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References

  1. Rodt H, Thierfelder S, Eulitz M . Anti-lymphocyte antibodies and marrow transplantation Eur J Immunol 1974 4: 15–19

    Article  CAS  Google Scholar 

  2. Reisner Y, Kapoor N, Kirkpatrick D et al. Transplantation for acute leukemia with HLA-A and B nonidentical parental marrow cells fractionated with soybean agglutinin and sheep red blood cells Lancet 1981 2: 327–331

    Article  CAS  Google Scholar 

  3. Filipovich AH, Vallera DA, Youle RJ et al. Ex vivo T cell depletion with immunotoxins in allogeneic bone marrow transplantation: the pilot clinical study for prevention of graft-versus-host disease Transplant Proc 1985 17: 442–444

    Google Scholar 

  4. Soderling CCB, Song CW, Blazar BR, Vallera DA . A correlation between conditioning and engraftment in recipients of MHC-mismatched T cell-depleted murine bone marrow transplants J Immunol 1985 135: 941–946

    CAS  PubMed  Google Scholar 

  5. O'Reilly RJ, Collins NH, Kernan N et al. Transplantation of marrow depleted of T cells by soybean lectin agglutination and E-rosette depletion: major histocompatibility complex-related graft resistance in leukemic transplant recipients Transplant Proc 1985 17: 455–459

    Google Scholar 

  6. Martin PJ, Hansen JA, Torok-Storb B et al. Graft failure in patients receiving T cell-depleted HLA-identical allogeneic marrow transplants Bone Marrow Transplant 1988 3: 445–456

    CAS  PubMed  Google Scholar 

  7. Poynton CH . T cell depletion in bone marrow transplantation Bone Marrow Transplant 1988 3: 265–279

    CAS  PubMed  Google Scholar 

  8. Horovitz MM, Gale RP, Sondel PM et al. Graft-versus-leukemia reactions after bone marrow transplantation Blood 1990 75: 555–562

    Google Scholar 

  9. Anasetti C, Amos D, Beatty PG et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma New Engl J Med 1989 320: 197–204

    Article  CAS  Google Scholar 

  10. Sykes M, Romick M, Sachs DH . Interleukin 2 prevents graft-versus-host disease while preserving the graft-versus-leukemia effect of allogeneic T cells Proc Natl Acad Sci USA 1990 87: 5633–5637

    Article  CAS  Google Scholar 

  11. Sykes M, Romick ML, Hoyles KA, Sachs DH . In vivo administration of interleukin 2 plus T cell-depleted syngeneic marrow prevents graft-versus-host disease mortality and permits alloengraftment J Exp Med 1990 171: 645–658

    Article  CAS  Google Scholar 

  12. Sykes M, Pearson DA . Alloengraftment in IL-2-treated mice Bone Marrow Transplant 1992 10: 157–163

    CAS  PubMed  Google Scholar 

  13. Sykes M, Abraham VS, Harty MW, Pearson DA . IL-2 reduces graft-versus-host disease and preserves a graft-versus-leukemia effect by selectively inhibiting CD4+ T cell activity J Immunol 1993 150: 197–205

    CAS  PubMed  Google Scholar 

  14. Sprent J, Scheafer M, Gao E, Korngold R . Role of T cell subsets in lethal graft versus host disease (GVHD) directed to class I versus class II H-2 differences. I. L3T4+ cells can either augment or retard GVHD elicited by Lyt-2+ cells in a class I-different host J Exp Med 1988 167: 556–569

    Article  CAS  Google Scholar 

  15. Malkovski M, Brenner MK, Hunt R et al. T-cell depletion of allogeneic bone marrow prevents acceleration of graft-versus-host disease induced by exogenous interleukin-2 CellImmunol 1986 103: 476–480

    Google Scholar 

  16. Jadus MR, Peck AB . Lethal murine graft-versus-host disease in absence of detectable cytotoxic T lymphocytes Transplantation 1983 36: 281–289

    Article  CAS  Google Scholar 

  17. Nakajima K, Smith CV, Mixon A et al. In vitro and in vivo effect of recombinant human IL-2 in miniature swine J Im-munother 1992 11: 169–175

    CAS  Google Scholar 

  18. Lunney JK, Pescovitz MD, Sachs DH . The swine major histocompatibility complex: Its structure and function. In: Tumbleson ME (ed) Swine in Biomedical Research Plenum Press: New York 1986 pp 1821–1836

    Google Scholar 

  19. Pennington LR, Sakamoto K, Popitz-Bergez FA et al. Bone marrow transplantation in miniature swine. I. Development of the model Transplantation 1988 45: 21–26

    Article  CAS  Google Scholar 

  20. Thomas ED, Storb R, Clift RA et al. Bone-marrow transplantation New Engl J Med 1975 292: 895–902

    Article  CAS  Google Scholar 

  21. Sykes M, Harty MW, Pearson D . Strain dependence of IL-2-induced GVHD protection: evidence that IL-2 inhibits selected CD4 function J Immunother 1994 15: 11–21

    Article  CAS  Google Scholar 

  22. Szebeni J, Wang M-G, Pearson DA et al. IL-2 inhibits early increases in serum gamma interferon levels associated with graft-vs-host disease Transplantation 1994 58: 1385–1393

    CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Drs Gary Haller and Yasushi Fuchimoto for their helpful reviews of the manuscript, and Lisa A Bernardo for help in manuscript preparation. This work was supported by a National Institutes of Health Grant No. 1 RO1 CA61537 and by a Sponsored Research Agreement between the Massachusetts General Hospital and BioTransplant, Inc. T Kozlowski is a recipient of a Sandoz Fellowship in Transplantation Award sponsored by the American Society of Transplant Physicians.

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Kozlowski, T., Sablinski, T., Basker, M. et al. Decreased graft-versus-host disease after haplotype mismatched bone marrow allografts in miniature swine following interleukin-2 treatment. Bone Marrow Transplant 25, 47–52 (2000). https://doi.org/10.1038/sj.bmt.1702083

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