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Pre-Clinical Studies

Interleukin-7 induced facilitation of immunological reconstitution of sublethally irradiated mice following treatment with alloreactive spleen cells in a murine model of B-cell leukemia/lymphoma (BCL1)

Abstract

Interleukin-7 (IL-7) plays a key role in maturation and function of both T and B cells. We investigate the potential use of recombinant human IL-7 for facilitation of graft-versus-leukemia (GVL) effects mediated by T cells following transplantation in a murine model. Administration of IL-7 in vivo to allogeneic-transplanted mice improved disease-free survival: 67% of mice treated with IL-7 remained alive and disease free for more than 60 days, in comparison to 17% of the controls (P<0.05). Similar results were obtained when C57BL/6 spleen cells sensitized against irradiated B-cell leukemia (BCL1) cells in the presence of IL-7 were transplanted to F1 mice, followed by IL-7 treatment in vivo. Of the BALB/c mice that received spleen cells from F1 mice treated with IL-7 following transplantation of C57BL/6 spleen cells sensitized with irradiated BCL1 in the presence of IL-7, only 29% developed leukemia, as compared to 79% in the control group (P<0.05). Mice treated with IL-7 showed increased splenic and thymic cellularity and improved T cell-dependent proliferative responses compared to the controls (P<0.05). IL-7 may provide a novel tool to enhance immune reconstitution following transplantation of mismatched stem cells and for enhancement of GVL effects mediated by alloreactive lymphocytes.

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References

  1. Truitt R, Johnson B, McCabe C, Weiler M . Graft-versus-leukemia. In: Ferrara J, Deeg H, Bukaroff S (eds). Graft-vs-Host Disease, 2nd edn. Marcel Dekker Inc.: New York, 1997, pp 385–424.

    Google Scholar 

  2. Barnes DHW, Loutit JF . Treatment of murine leukaemia with x-rays and homologous bone marrow. II. Br J Haematol 1957; 3: 241–252.

    Article  CAS  Google Scholar 

  3. Mathé G, Amiel JL, Schwarzenberg L, Cattan A, Schneider M, Devries MJ et al. Successful allogeneic bone marrow transplantation in man: chimerism, induced specific tolerance and possible antileukemic effects. Blood 1965; 25: 179.

    PubMed  Google Scholar 

  4. Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED . Anti-leukemic effect of chronic graft-versus-host-disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 1981; 304: 1529–1531.

    Article  CAS  Google Scholar 

  5. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  Google Scholar 

  6. Fry TJ, Mackall CL . Interleukin-7: from bench to clinic. Blood 2002; 99: 3892–3904.

    Article  CAS  Google Scholar 

  7. Sempowski GD, Gooding ME, Liao HX, Le PT, Haynes BF . T cell receptor excision circle assessment of thymopoiesis in aging mice. Mol Immunol 2002; 38: 841–848.

    Article  CAS  Google Scholar 

  8. Bolotin E, Smogorzewska M, Smith S, Widmer M, Weinberg K . Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7. Blood 1996; 88: 1887–1894.

    CAS  PubMed  Google Scholar 

  9. Okamoto Y, Douek DC, McFarland RD, Koup RA . Effects of exogenous interleukin-7 on human thymus function. Blood 2002; 99: 2851–2858.

    Article  CAS  Google Scholar 

  10. Geiselhart LA, Humphries CA, Gregorio TA, Mou S, Subleski J, Komschlies KL . IL-7 administration alters the CD4:CD8 ratio, increases T cell numbers, and increases T cell function in the absence of activation. J Immunol 2001; 166: 3019–3027.

    Article  CAS  Google Scholar 

  11. Lynch DH, Miller RE . Interleukin 7 promotes long-term in vitro growth of antitumor cytotoxic T lymphocytes with immunotherapeutic efficacy in vivo. J Exp Med 1994; 179: 31–42.

    Article  CAS  Google Scholar 

  12. Wiryana P, Bui T, Faltynek CR, Ho RJ . Augmentation of cell-mediated immunotherapy against herpes simplex virus by interleukins: comparison of in vivo effects of IL-2 and IL-7 on adoptively transferred T cells. Vaccine 1997; 15: 561–563.

    Article  CAS  Google Scholar 

  13. Abdul-Hai A, Or R, Slavin S, Friedman G, Weiss L, Matsa D et al. Stimulation of immune reconstitution by interleukin-7 after syngeneic bone marrow transplantation in mice. Exp Hematol 1996; 24: 1416–1422.

    CAS  PubMed  Google Scholar 

  14. Alpdogan O, Schmaltz C, Muriglan SJ, Kappel BJ, Perales MA, Rotolo JA et al. Administration of interleukin-7 after allogeneic bone marrow improves immune reconstitution without aggravating graft-versus-host disease. Blood 2001; 98: 2256–2265.

    Article  CAS  Google Scholar 

  15. Mackall CL, Fry TJ, Bare C, Morgan P, Galbraith A, Gress RE . IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration after bone marrow transplantation. Blood 2001; 97: 1491–1497.

    Article  CAS  Google Scholar 

  16. Slavin S, Strober S . Spontaneous murine B-cell leukaemia. Nature 1978; 272: 624–626.

    Article  CAS  PubMed Central  Google Scholar 

  17. Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998; 339: 1186–1193.

    Article  CAS  Google Scholar 

  18. Aversa F, Velardi A, Tabilio A, Reisner Y, Martelli MF . Haploidentical stem cell transplantation in leukemia. Blood Rev 2001; 15: 111–119.

    Article  CAS  Google Scholar 

  19. Or R, Abdul-Hai A, Ben-Yehuda A . Reviewing the potential utility of interleukin-7 as a promoter of thymopoiesis and immune recovery. Cytokines Cell Mol Ther 1998; 4: 287–294; Review.

    CAS  PubMed  Google Scholar 

  20. Abdul-Hai A, Weiss L, Slavin S, Or R . Improved survival following induction of GVHD following lipopolysaccharide immunization. Exp Hematol 2006; 34: 549–553.

    Article  CAS  Google Scholar 

  21. Weiss L, Reich S, Slavin S . Allogeneic cell therapy in murine B-cell leukemia (BCL1): 2. The role of non-activated and rIL-2-activated CD4+ and CD8+ T cells in immunotherapy for leukemia. Cytokines Cell Mol Ther 1999; 5: 153–158.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the Danny Cunniff Leukemia Research Laboratory for its continuous support of our ongoing basic and clinical research.

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Correspondence to S Slavin.

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Abdul-Hai, A., Weiss, L., Ben-Yehuda, A. et al. Interleukin-7 induced facilitation of immunological reconstitution of sublethally irradiated mice following treatment with alloreactive spleen cells in a murine model of B-cell leukemia/lymphoma (BCL1). Bone Marrow Transplant 40, 881–889 (2007). https://doi.org/10.1038/sj.bmt.1705819

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