Skip to main content
Log in

Deficient expression of class-I HLA in some cases of acute leukemia

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

Summary

Leukemic cells from the blood and marrow of 25 cases of newly diagnosed acute leukemia were presented as target cells to alloreactive effector cells from unrelated normal donors in cell-mediated cytotoxicity assays. In three cases the leukemic targets were poorly killed relative to nonleukemic, HLA-identical target cells. The poor killing of the leukemic cells from one of these cases was shown by competitive inhibition to be due to deficient expression of normal class-I HLA antigens rather than resistance to lysis. Furthermore, the leukemic cells from these three patients were also deficient in binding monoclonal antibodies to nonpolymorphic determinants of class-I HLA and B2 microglobulin. Two additional cases were identified as having a less extensive deficit of HLA, and may be representative of a group with relatively subtle changes in these cell surface antigens. The possible significance of reduced expression of HLA in leukemic progression and in susceptibility to graft-vs-leukemia reactions after bone marrow transplantation is discussed.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bernards R, Schrier PI, Houweling A, Bos JL, van der Ef AH, Ziglstra M, Melief CJM (1983) Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity. Nature 305:776

    Google Scholar 

  2. Bhan AK, Reinherz EL, Poppena S, McCloskey RT, Schlossman SF (1980) Location of T cell and major histocompatibility complex antigens in the human thymus. J Exp Med 152:771

    Google Scholar 

  3. Boyd HC, Potter TA, Rajan TV, Zmijewski CM, McKearn TC (1983) A rodent class I MHC determinant is shared among many species. Immunogenetics 18:183–187

    Google Scholar 

  4. Bradstock KF, Janossy G, Bollum FJ, Milstein C (1980) Anomolous phenotype in thymic acute lymphoblastic leukemia. Nature 284:455–457

    Google Scholar 

  5. Clarke MF, Gelmann EP, Reitz MS (1983) Homology of human T-cell leukemic virus envelope gene with class I HLA gene. Nature 305:60

    Google Scholar 

  6. Eijsvogel VP (1974) Cellular recognition in vitro of antigens related to human histocompatibility. Semin Hematol 11:305–324

    Google Scholar 

  7. Fitchen JH, Foon KA, Cline MJ (1981) Antigenic characteristics of hemopoietic stem cells. N Engl J Med 305:17

    Google Scholar 

  8. Fulwyler MJ, McDonald CW, Heynes JJ (1979) The Becton Dickinson cell sorter. In: Melamed M, Mullany P, Mendelsohn M (eds) Flow cytometry and cell sorting. Wiley, New York, pp 653–667

    Google Scholar 

  9. Gooding LR (1982) Characterization of a progressive tumor from C3H fibroblasts transformed in vitro with SV40 virus. Immunoresistance in vivo correlates with phenotypic loss of H2-Kk. J Immunol 129:1306–1312

    Google Scholar 

  10. Greenberg PD, Cheever MA (1983) Reactivity of syngeneic and allogeneic cells against tumor. In: Gale RP (ed) Recent advances in bone marrow transplantation. Liss, New York, p 255–279

    Google Scholar 

  11. Lampson LA, Fisher CA, Whelan JP (1983) Striking paucity of HLA-A,B,C and b2-microglobulin on human neuroblastoma cell lines. J Immuno 130:2471

    Google Scholar 

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

    Google Scholar 

  13. Mann DL, Popovic M, Sarin P, Murray C, Reitz MS, Strong DM, Haynes BF, Gallo RC, Blattner WA (1983) Cell lines producing human T cell lymphoma virus show altered HLA expression. Nature 305:58

    Google Scholar 

  14. Martinis J, Bach FH (1978) HLA CD antigen crossmatching — the pool cell-mediated lympholysis test. Transplantation 25:39

    Google Scholar 

  15. Mitsuya H, Matis LA, Megsou M, Bunn PA, Murray C, Mann DL, Gallo RC, Broder S (1983) Generation of an HLA-restricted cytotoxic T cell line reactive against cultured tumor cells from a patient infected with human T cell leukemia/lymphoma virus. J Exp Med 158:994

    Google Scholar 

  16. Pierson GR, Elkins WL (1981) Recognition of HLA and minor alloantigens on human target cells by allostimulated cytotoxic effectors in vitro. Transplant Proc 13:1901

    Google Scholar 

  17. Pierson GR, Elkins WL (1983) In vitro generation of cytotoxic cells with graft-versus-host specificity from the blood of patients with graft-versus-hos disease. These effectors may detect minor alloantigens on leukemic targets from the host. In: Gale RP (ed) Recent advances in bone marrow transplantation. Liss, New York, pp 223–226

    Google Scholar 

  18. Sanderson AR, Beverly PCL (1983) Interferon, B-2-microglobulin, and immunoselection in the pathway to malignancy. Immunol Today 4:211

    Google Scholar 

  19. Schmidt W, Festenstein H (1982) Resistance to cellmediated cytotoxicity is correlated with reduction of H-2K gene products in AKR leukemia. Immunogenetics 16:257–264

    Google Scholar 

  20. Seigler HD, Kremer WB, Metzgar RS, Ward FE, Hwang AT, Amos DB (1971) HLA antigenic loss in malignant transformation. J.N.C.I. 46:577

    Google Scholar 

  21. Smilek DE, Boyd HC, Wilson DB, Zmijewski CM, Fitch FW, McKearn TJ (1980) Monoclonal rat anti-major histocompatibility complex antibodies display specificity for rat, mouse, and human target cells. J Exp Med 151:1139–1150

    Google Scholar 

  22. Sondel PM, Bach FH (1975) Recognitive specificity of human cytotoxic T lymphocytes. J Exp Med 142:1339

    Google Scholar 

  23. Taylor GM, Bradley BA (1983) The role of allogeneic cells in the stimulation of cell-mediated cytotoxicity to leukemia cells. A family study. Cancer Immunol Immunother 15:39

    Google Scholar 

  24. Truitt RL, Shik CY, Kaebler DA, Le Fever AV, Bortin MM (1983) Graft-versus-leukemia and graft-versus-host reactivity following alloimmunization of MHC-compatible donor mice. In: Gale RP (ed) Recent advances in bone marrow transplantation. Liss, New York, pp 243–253

    Google Scholar 

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

    Google Scholar 

  26. Zier KS, Elkins WL, Pierson GR (1982) Cytotoxic T lymphocyte lines against a human minor alloantigen. Immunogenetics 15:501

    Google Scholar 

  27. Zinkernagel RM, Doherty PC (1979) MHC-restricted cytotoxic T cells. Studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol 27:51

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Elkins, W.L., Pickard, A. & Pierson, G.R. Deficient expression of class-I HLA in some cases of acute leukemia. Cancer Immunol Immunother 18, 91–100 (1984). https://doi.org/10.1007/BF00205741

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00205741

Keywords

Navigation