Skip to main content

Advertisement

SpringerLink
Log in

The role of allogeneic cells in the stimulation of cell-mediated cytotoxicity to leukaemia cells

A family study

  • Original Articles
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Summary

Allogeneic lymphocytes can stimulate cell-mediated cytotoxicity (CMC) in lymphocytes from leukaemia patients against autologous leukaemia target cells. We have compared the capacity of different allogeneic lymphoid cells to stimulate CMC to fresh (i.e., patient) and cultured (MOLT 4, K562) leukaemic target cells in lymphocytes from an acute leukaemic patient and his HLA-identical siblings. Allogeneic lymphoid cells, and particularly a lymphoblastoid cell line, were effective in stimulating CMC to leukaemia targets. In some instances, however, leukaemia cells derived from the patient, mixed with allogeneic lymphoid cells stimulated synergistic CMC to the patient's leukaemia. We also found that the patient's leukaemia cells alone were able to stimulate CMC in HLA-identical sib lymphocytes to fresh and cultured leukaemia targets. Extra specificities on fresh leukaemia cells were revealed when these cells induced unpredicted CMC on normal lymphocyte targets when added to mixed lymphocyte cultures (MLC) between related and unrelated lymphocytes. Cytotoxic lymphocytes generated in MLC against the patient's HLA antigens were absorbed by monolayers of lymphocytes and leukaemia cells of the same HLA type as the patient, leaving residual CMC to fresh (patient) and cultured (K562) leukaemia target cells. In addition, CMC to the patient's leukaemia cells, stimulated in lymphocytes from the patient's HLA-identical sib by allogeneic cells, was absorbed by a monolayer of these allogeneic cells. This suggests cross reactivity between determinants on the leukaemia and allogeneic lymphocytes. The results of this study are consistent with expression of ‘leukamia antigens’, which are not restricted to leukaemia cells but may also be expressed on lymphocytes.

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. Anderson PN, Klein DL, Bias WB, Mullins GM, Burke PJ, Santos GW (1974) Cell-mediated immunological reactivity of patients and siblings to blast cells from adult acute leukaemias. Isr J Med Sci 10:1033

    Google Scholar 

  2. Andersson LA, Nilsson K, Gahmberg CG (1979) K562. A human erythroleukaemic cell line. Int J Cancer 23:143

    Google Scholar 

  3. Hamilton JD, Bradley BA, Van Rood JJ (1979) Monolayer absorption of human cytotoxic T cells: evidence for clonality. Tissue Antigens 13:349

    Google Scholar 

  4. Han T, Minowada J (1973) A unique ‘leukaemic’ T lymphoid cell line: absence of stimulating effect in mixed lymphocyte reaction. Lack of MLR-S in leukaemic T lymphoid cells. Clin Exp Immunol 15:535

    Google Scholar 

  5. Herberman RB, Holden HT (1978) Natural cell-mediated immunity. Adv Cancer Res 27:305

    Google Scholar 

  6. Herberman RB, McCoy JL, Levine PH (1974) Immunological reactions to tumour-associated antigens in Burkitt's lymphoma and other lymphomas. Cancer Res 34:1222

    Google Scholar 

  7. Herberman RB, Djeu JY, Kay HD et al. (1979) Natural killer cells: Characteristics and regulation of activity. Immunol Rev 44:42

    Google Scholar 

  8. Jensen PJ, Amos DB, Koren HS (1979) Depletion of NK by cellular immunoabsorption. J Immunol 123:1127

    Google Scholar 

  9. Klein E, Vanky F (1981) Natural and activated cytotoxic lymphocytes which act on autologous and allogeneic tumour cells. Cancer Immunol Immunother 11:183

    Google Scholar 

  10. Klein E (1981) Central issues in present day tumour immunology: interpretation of lymphocytotoxicity assays and the demonstration of auto-tumor-reactive lymphocytes in patients. In: Monaco AP, Wood ML, Rapaport FT (eds) Transplantation today, vol VI. Grune & Stratton, New York London, p 723

    Google Scholar 

  11. Lee SK, Oliver RTD (1978) Autologous leukaemia-specific T cell-mediated lymphocytotoxicity in patients with acute myelogenous leukaemia. J Exp Med 147:912

    Google Scholar 

  12. Levy RB, Gilheany PE, Shearer GM (1980) Role of self and foreign antigenic determinants in allogeneic and self-restricted cytotoxic T-cell recognition. J Exp Med 152:405

    Google Scholar 

  13. Masucci MG, Klein G, Argov S (1980) Disappearance of the NK effect after explantation of lymphocytes and generation of similar non-specific cytotoxicity correlated to the level of blastogenesis in activated cultures. J Immunol 124:2458

    Google Scholar 

  14. Moore M, Potter MR (1980) Enhancement of human natural cell mediated cytotoxicity by interferon. Br J Cancer 41:378

    Google Scholar 

  15. Moore M, Taylor GM, White WJ (1982) Susceptibility of human leukaemias to cell-mediated cytotoxicity by interferon-treated allogeneic lymphocytes. Cancer Immunol Immunother 13:56–61

    Google Scholar 

  16. Ortaldo JR, Bonnard GD (1977) Presence of natural killer cell activity in cytotoxic lymphocytes from MLC-CML reactions. Fed Proc 36:1352

    Google Scholar 

  17. Rosenberg EB, Herberman RB, Levine PH, Halterman RH, McCoy JL, Wunderlich JR (1972) Lymphocyte cytotoxicity reactions to leukaemia-associated antigens in identical twins. Int J Cancer 9:648

    Google Scholar 

  18. Seeley JK, Golub SH (1978) Studies on cytotoxicity generated in human mixed lymphocyte cultures. Time curve and target spectrum of several distinct concomitant cytotoxic activities. J Immunol 120:1415

    Google Scholar 

  19. Sondel PM, Hank JA (1981) Alien-driven diversity and alien-selected escape: a rationale for allogeneic cancer immunotherapy. Transplant Proc 12:1915

    Google Scholar 

  20. Sondel PM, O'Brien C, Porter L, Schlossman SF, Chess L (1976) Cell-mediated destruction of human leukaemic cells by MHC identical lymphocytes; requirement for a proliferative trigger in vitro. J Immunol 117:2197

    Google Scholar 

  21. Taylor GM (1981) In vitro stimulation of cell-mediated cytotoxicity by acute leukaemias. Br J Cancer 43:157

    Google Scholar 

  22. Taylor GM, Bradley BA (1979) Graft-versus-leukaemia without graft versus host? Lancet 2:959

    Google Scholar 

  23. Taylor GM, Zuhrie SR, Harris R (1979) Cell-mediated cytotoxicity in relation to active immunotherapy in acute myeloid leukaemia. Cancer Immunol Immunother 5:263

    Google Scholar 

  24. Vanky F, Argov S, Klein E (1981) Tumour biopsy cells participating in systems in which cytotoxicity of lymphocytes is generated. Autologous and allogeneic studies. Int J Cancer 27:273

    Google Scholar 

  25. Van Rood JJ, van Leeuwen A, Ploem JS (1976) Simultaneous detection of two cell populations by two-colour fluorescence and application to the recognition of B cell determinants. Nature 262:795

    Google Scholar 

  26. Wieden PH, Flournoy N, Thomas ED, et al. (1979) Anti-leukaemic effect of graft-versus-host disease in human recipients of allogeneic marrow grafts. N Engl J Med 300:1068

    CAS  PubMed  Google Scholar 

  27. Zarling JM, Bach FH (1978) Sensitisation of lymphocytes against pooled allogeneic cells. 1. Generation of cytotoxicity against autologous human lymphoblastoid cell lines. J Exp Med 147:1334

    Google Scholar 

  28. Zarling JM, Raich PC, McKeough M, Bach FH (1976) Generation of cytotoxic lymphocytes in vitro against autologous human leukaemia cells. Nature 262:691

    Google Scholar 

  29. Zarling JM, Robins HI, Raich PC, Bach FH, Bach ML (1978) Generation of cytotoxic T-lymphocytes to autologous human leukaemia cells by sensitisation to pooled allogeneic normal cells. Nature 274:269

    Google Scholar 

  30. Zarling JM, Eskra L, Borden EC, Horoszewicz J, Carter WA (1979) Activation of human natural killer cells cytotoxic for human leukaemic cells by purified interferon. J Immunol 123:63

    Google Scholar 

  31. Zarling JM, Bach FH, Kearney PC (1981) Sensitisation of lymphocytes against pooled allogeneic cells. II. Characterisation of effector cells cytotoxic for autologous lymphoblastoid cell-lines. J Immunol 126:375

    Google Scholar 

  32. Zier KS, Huber C, Albert E, Braunsteiner H (1980) Cell-mediated immune responses between HLA-identical siblings: recognition of antigenic changes associated with acute myelogeneous leukaemia. Clin Exp Immunol 40:136

    Google Scholar 

  33. Zuhrie SR, Harris R, Freeman CB, et al. (1980) Immunotherapy alone vs no maintenance treatment in acute myelogenous leukaemia. Br J Cancer 41:372

    Google Scholar 

Download references

Author information

Author notes

  1. G. M. Taylor

    Present address: Department of Medical Genetics, St Mary's Hospital, University of Manchester, M13 OJH, Manchester, England

Authors and Affiliations

  1. Department of Immunohaematology, Academish Ziekenhuis, University of Leiden, Leiden, Holland

    G. M. Taylor & B. A. Bradley

Authors
  1. G. M. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. A. Bradley
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Present address: U. K. Transplant Service, South West Regional Blood Transfusion Service, South West Regional General Hospital, Southmead, Bristol, England

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taylor, G.M., Bradley, B.A. The role of allogeneic cells in the stimulation of cell-mediated cytotoxicity to leukaemia cells. Cancer Immunol Immunother 15, 39–46 (1983). https://doi.org/10.1007/BF00199460

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00199460

Keywords

Search

Navigation