Skip to main content
SpringerLink
Log in

Gaft-versus-leukemia activity after bone marrow transplantation does not require graft-versus-host disease

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Summary

Clinical data have suggested that graft-versus-host disease (GVHD) plays a crucial role in the antileukemic effects of bone marrow grafts. We investigated (a) whether bone marrow cells unable to induce GVHD can effect graft-versus-leukemia (GVL) activity and (b) whether such antileukemic capacity depends on the presence of T lymphocytes in the graft. Balb/c mice were inoculated with A 20 cells, a B-cell lymphoma/leukemia of Balb/c origin. Four weeks after tumor inoculation the animals were lethally irradiated and received a bone marrow graft. Cells from (Balb/c × C57) F1 or (C3H × Balb/c) F1 hybrids were transplanted into parental-strain Balb/c mice. Since lymphocytes from F1 hybrids are unable to cause graft-versus-host reactivity against a parental-strain animal, we used this experimental setting to explore GVL effects in a GVHD-free system. In vitro incubation with monoclonal anti-Thy-1.2 antibody plus complement was used to eliminate Thy-1+ cells. After syngeneic transplantation, the death rate due to leukemia remained unchanged (91%) compared with that among untreated animals (86%). Following transplantation of F1 marrow cells of either (C57 × Balb/c) F1 or (C3 H × Balb/c) F1 origin, death rates of 40% and 50% were observed; these were significantly lower. Depletion of Thy 1+ cells from bone marrow graft caused only a slight increase in the leukemic death rate after transplantation of bone marrow of (C57 × Balb/c) F1 hybrid origin (50%), but a high leukemic death rate was seen after transplantation of (C3H × Balb/c) F1 bone marrow (100%). Additional experiments with fully allogeneic, T-cell-depleted C57 bone marrow transplantation suggest an antileukemic effect that is comparable to that seen after transplantation of unmanipulated F1 bone marrow. Taken together, our results indicate that GVL activity can be dissociated from graft-versus-host reaction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Atkinson K (1990) Chronic graft-versus-host disease. Bone Marrow Transplant 5: 69–82

    PubMed  Google Scholar 

  2. Atkinson K, Farrelly H, Cooley MA, O'Flaherty E, Downs K, Biggs J (1987) Human marrow T-cell dose correlates with severity of subsequent acute graft-versus-host disease. Bone Marrow Transplant 2: 51–57

    PubMed  Google Scholar 

  3. Bortin MM, Horowitz MM, Gale RP (1989) Current status of bone marrow transplantation in humans: report from the international bone marrow transplant registry. Nat Immun Cell Growth Regul 7: 334–350

    Google Scholar 

  4. Bortin MM, Truitt RL, Rimm AA, Bach FH (1979) Graft-versus-leukaemia reactivity induced by alloimmunisation without augmentation of graft-versus-host reactivity. Nature 281: 490–491

    PubMed  Google Scholar 

  5. Butturini A, Gale RP (1989) How can we cure leukaemia. Br J Haematol 72: 479–485

    PubMed  Google Scholar 

  6. Champlin R, Ho W, Gajewski J, Feig S, Burnison M, Holley G, Greenberg P, Lee K, Schmid I, Giorgi J, Yam P, Petz L, Winston D, Warner N, Reichert T (1990) Selective depletion of CD 8+T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation. Blood 76: 418–423

    PubMed  Google Scholar 

  7. Cudkowicz G, Bennett M (1971) Peculiar immunobiology of bone marrow allografts. II. Rejection of parental grafts by resistant F1 hybrid mice. J Exp Med 134: 1513–1528

    PubMed  Google Scholar 

  8. Dady PJ, Nakamura I (1984) Natural resistance of lethally irradiated F1 hybrid mice to parental marrow grafts is a function of H-2/Hh-restricted effectors. J Exp Med 159: 1132–1148

    PubMed  Google Scholar 

  9. Fefer A, Einstein AB Jr, Cheever MA, Berenson RJ (1976) Models for syngeneic adoptive immunotherapy of murine leukemias. Ann NY Acad Sci 276: 573–583

    PubMed  Google Scholar 

  10. Hauch M, Gazzola MV, Small T, Bordignon C, Barnett L, Cunningham I, Castro Malaspinia H, O'Reilly RJ, Keever CA (1990) Anti-leukemia potential of interleukin-2-activated natural killer cells after bone marrow transplantation for chronic myelogenous leukemia. Blood 75: 2250–2262

    PubMed  Google Scholar 

  11. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb H-J, Rimm AA, Ringén O, Rozman C, Speck B, Truitt RL, Zwaan FE, Bortin MM (1990) Graft-versus-leukemia reactions after bone marrow transplantation. Blood 75: 555–562

    PubMed  Google Scholar 

  12. Kim KJ, Kannellopoulus-Langevin C, Mervin RM, Sachs DH, Asofsky R (1979) Establishment and characterization of Balb/c lymphoma lines with B-cell properties. J Immunol 122: 549–554

    PubMed  Google Scholar 

  13. Kosmatopoulos K, Scott-Algara D, Halle-Pannenko O (1988) Specific inhibition of hybrid resistance in F1 hybrid mice pretreated with parent-strain spleen cells. II. Evidence for an Hh-1 antigen-specific tolerization. J Immunol 141: 3285–3292

    PubMed  Google Scholar 

  14. Lotzova E, Savary CA (1983) Natural resistance to foreign hemopoietic transplants: a possible model of leukemia surveillance. Prog Clin Biol Res 132: 125–135

    Google Scholar 

  15. Lotzova E, Savary CA, Herberman RB (1987) Inhibition of clonogenic growth of fresh leukemia cells by unstimulated and IL-2-stimulated NK cells of normal donors. Leuk Res 11: 1059–1066

    PubMed  Google Scholar 

  16. Marshak-Rothenstein A, Fink P, Gridley T, Raulet DH, Bevan MJ, Gefter ML (1979) Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 Locus. J Immunol 122: 2391–2497

    Google Scholar 

  17. Mayer RJ (1990) Acute leukemias in adults: an overview of recent strategies. J Cancer Res Clin Oncol 116: 94–96

    PubMed  Google Scholar 

  18. Meredith RF, O'Kunewick JP (1983) Possibility of graft-vs-leukemia determinants independent of the major histocompatibility complex in allogeneic marrow transplantation. Transplantation 35: 378–385

    PubMed  Google Scholar 

  19. O'Kunewick JP, Meredith RF, Raikow RB, Brozovich BJ, Magliere K (1981) Graft-vs-leukemia and moderation of graft-vs-host reaction in transplantation therapy of viral leukemia. Exp Hematol 9: 754–765

    PubMed  Google Scholar 

  20. Savary CA, Lotzová E (1989) Natural killer cell-mediated inhibition of growth of myeloid and lymphoid clonogenic leukemias. Exp Hematol 17: 183–187

    PubMed  Google Scholar 

  21. Slavin S, Weiss L, Morecki S, Weigensberg M (1981) Eradication of murine leukemia with histoincompatible marrow grafts in mice conditioned with total lymphoid irradiation. Cancer Immunol Immunother 11: 155–161

    Google Scholar 

  22. Sullivan KM, Storb R, Buckner CD, Fefer A, Fisher L, Weiden PL, Witherspoon RP, Appelbaum FR, Banaji M, Hansen J, Martin P, Sanders JE, Singer J, Thomas ED (1989) Graftversus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms. N Engl J Med 320: 828–834

    PubMed  Google Scholar 

  23. Sykes M, Sachs DH (1989) Genetic analysis of the antileukemic effect of mixed allogeneic bone marrow transplantation. Transplant Proc 21: 3022–3024

    PubMed  Google Scholar 

  24. Truitt RL, Shih CY, Le Fever AV, Tempelis LD, Andreani M, Bortin MM (1983) Characterization of alloimmunization-induced T lymphocytes reactive against AKR leukemia in vitro and correlation with graft-vs-leukemia activity in vivo. J Immunol 131: 2050–2058

    PubMed  Google Scholar 

  25. Weiden PL, Flournoy MS, Thomas ED, Prentice R, Fefer A, Buckner CD, Storb R (1979) Antileukemic effect of graftversus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med 300: 1068–1073

    PubMed  Google Scholar 

  26. Weiss L, Morecki S, Vitetta ES, Slavin S (1983) Suppression and elimination of BCL1 leukemia by allogeneic bone marrow transplantation. J Immunol 130: 2452–2455

    PubMed  Google Scholar 

  27. Welte K, Keever CA, Levick J, Bonilla MA, Merluzzi VJ, Mertelsmann R, Evans R, O'Reilly RJ (1987) Interleukin-2 production and response to interleukin-2 by peripheral blood mononuclear cells from patients after bone marrow transplantation. II. Patients receiving soybean lectin-separated and T-cell-depleted bone marrow. Blood 70: 1595–1603

    PubMed  Google Scholar 

  28. Westcott O, Dorsch S, Roser B (1979) Adoptive immunotherapy of leukemia in the rat, without graft-versus-host complications. J Immunol 123: 1478–1483

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Immunology and Department of Internal Medicine II, University of Kiel, Germany

    B. Glass, L. Uharek, W. Gassmann, B. Focks, H. Bolouri, H. Loeffler & W. Mueller-Ruchholtz

Authors
  1. B. Glass
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Uharek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Gassmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. Focks
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Bolouri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H. Loeffler
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. W. Mueller-Ruchholtz
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Glass, B., Uharek, L., Gassmann, W. et al. Gaft-versus-leukemia activity after bone marrow transplantation does not require graft-versus-host disease. Ann Hematol 64, 255–259 (1992). https://doi.org/10.1007/BF01695466

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01695466

Key words

Search

Navigation