Skip to main content
Log in

Generation of T cell clones binding F(ab′)2 fragments of the idiotypic immunoglobulin in patients with monoclonal gammopathy

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

Summary

Lymphocytes from two patients with multiple myeloma stage I and one patient with monoclonal gammopathy of undetermined significance were found to proliferate specifically in response to low concentrations of F(ab′)2 fragments of the autologous M component. T cell clones isolated from repeatedly stimulated cultures bound specifically the autologous idiotype and proliferated after addition of soluble idiotype and exogenous interleukin-2. The majority of clones were CD8+ and showed negligible staining for CD4. Idiotype-binding clones could not be isolated from cultures of lymphocytes from a healthy control stimulated under the same conditions. The study provides support for the existence of idiotype-reactive T cells in monoclonal gammopathies. Such cells might have a regulatory role on the tumour cell clone and may be important for a future therapeutic approach.

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. Altman DM, Lider O, Doueck DC, Cohen IR (1985) Activation of specific T cell lines by the antigens avidin and myelin basic protein in the absence of antigen-presenting cells. Eur J Immunol 17: 1635

    Google Scholar 

  2. Becker Dunn E, Bottomly K (1985) T15-specific helper T cells: analysis of idiotype-specificity by competitive inhibition analysis. Eur J Immunol 15: 728

    Google Scholar 

  3. Berenson J, Wong R, Kim K, Brown N, Lichtenstein A (1987) Evidence for peripheral blood B lymphocyte but not T lymphocyte involvement in multiple myeloma. Blood 70: 1550

    Google Scholar 

  4. Bergenbrant S, Österborg A, Holm G, Mellstedt H, Lefvert A-K (1991) Anti-idiotypic antibodies in patients with monoclonal gammopathies. Relation to the tumor load. Br J Haematol 78: 66

    Google Scholar 

  5. Bottomly K, Mosier DE (1981) Antigen specific helper T cells required for dominant idiotype expression are not H-2 restricted. J Exp Med 154: 411

    Google Scholar 

  6. Böyum A (1983) Isolation of human blood monocytes with Nycodenz, a new non-ionic iodinated gradient medium. Scand J Immunol 17: 429

    Google Scholar 

  7. Cerny J, Smith JS, Webb C, Tucker PW (1988) Properties of anti-idiotypic T cell lines propagated with syngeneic B lymphocytes: I. T cells bind intact idiotypes and discriminate between the somatic idiotypic variants in a manner similar to the anti-idiotypic antibodies. J Immunol 141: 3718

    Google Scholar 

  8. Daley MJ, Gebel HM, Lynch RG (1978) Idiotype-specific transplantation resistance to MOPC-315: abrogation by post-immunization thymectomy. J Immunol 120: 1620

    Google Scholar 

  9. Dianzani U, Pileri A, Boccadoro M, Palumbo A, Pioppo P, Bianchi A, Camponi A, Fossati G, Battaglio S, Massaia M (1988) Activated idiotype-reactive cells in suppressor/cytotoxic subpopulations of monoclonal gammopathies: correlation with diagnosis and disease status. Blood 72: 1064

    Google Scholar 

  10. Durie BGM, Salmon SE (1975) A clinical staging system for multiple myeloma. Cancer 36: 842

    Google Scholar 

  11. Flood PM, Philipps C, Taupier MA, Schreiber H (1980) Regulation of myeloma growth in vitro by idiotype-specific T lymphocytes. J Immunol 124: 424

    Google Scholar 

  12. Forni L (1979) Reagents for immunofluorescence and their use for studying lymphoid cell products: In: Lefkovits I (ed) Immunological methods. Academic Press, New York, p 151

    Google Scholar 

  13. Gramatzki M, Klusmann A, Kalden JR (1989) “Immune” T-lymphocytes expanded in vitro showing anti-myeloma cytotoxic activity. Meeting abstract. Proc Annu Meet Am Soc Clin Oncol 8: 253

    Google Scholar 

  14. Grey HM, Sette A, Buus S (1989) How T cells see antigen. Sci Am 261: 38

    Google Scholar 

  15. Janson CH, Grunewald J, Österborg A, DerSimonian H, Brenner MB, Mellstedt H, Wigzell H (1991) Predominant T cell receptor V gene usage in patients with abnormal clones of B cells. Blood 77: 1776

    Google Scholar 

  16. Jerne NK (1974) Towards a network theory of the immune system. Ann Immunol (Paris) 125C: 373

    Google Scholar 

  17. Jörgensen T, Hannestad K (1982) Helper T recognition of the variable domains of a mouse myeloma protein (315). J Exp Med 155: 1587

    Google Scholar 

  18. Lynch RG (1987) Immunoglobulin-specific suppressor T cells. Adv Immunol 40: 135

    Google Scholar 

  19. Lynch RG, Graff RJ, Sirisinha S, Simms ES, Eisen HN (1972) Myeloma proteins as tumor-specific transplantation antigens. Proc Natl Acad Sci USA 69: 1540

    Google Scholar 

  20. Lynch RG, Rohrer JW, Odermatt B, Gebel HM, Autry JR, Hoover RG (1979) Immunoregulation of murine myeloma cell growth and differention: a monoclonal model of B cell differention. Immunol Rev 48: 45

    Google Scholar 

  21. Mellstedt H, Björkholm M, Holm G (1977) Intermittent melphalan prednisone therapy in plasma cell myeloma. Acta Med Scand 202: 5

    Google Scholar 

  22. Mellstedt H, Holm G, Björkholm M (1984) Multiple myeloma, Waldenström's macroglobulinemia and benign monoclonal gammopathy. Characteristics of the B cell clone, immunoregulatory cell populations and clinical implications. Adv Cancer Res 41: 257

    Google Scholar 

  23. Milburn GL, Lynch RG (1982) Immunoregulation of murine myeloma in vitro: II. Suppression of MOPC-315 immunoglobulin secretion and synthesis by idiotype-specific suppressor T cells. J Exp Med 155: 852

    Google Scholar 

  24. Milburn GL, Lynch RG (1983) Anti-idiotypic regulation of IgA expression in myeloma cells. Mol Immunol 20: 931

    Google Scholar 

  25. Peest D, de Vries I, Hölscher R, Leo R, Deicher H (1989) Effect of interleukin-2 on the ex vivo growth of human myeloma cells. Cancer Immunol Immunother 30: 227

    Google Scholar 

  26. Pettersson D, Mellstedt H, Holm G (1978) IgG on human blood lymphocytes studied by immunofluorescence. Scand J Immunol 8: 535

    Google Scholar 

  27. Pettersson D, Mellstedt H, Holm G, Björkholm M (1981) Monoclonal blood lymphocytes in benign monoclonal gammopathy and multiple myeloma in relation to clinical stage. Scand J Haematol 27: 287

    Google Scholar 

  28. Saeki Y, Chen JJ, Shi L, Raychaudhuri S, Köhler H (1989) Characterization of “regulatory” idiotype-specific T cell clones to a monoclonal anti-idiotypic antibody mimicking a tumor-associated antigen (TAA). J Immunol 142: 1046

    Google Scholar 

  29. Selvan RS, Nagarkatti PS, Nagarkatti M (1990) Role of IL-2, IL-4 and IL-6 in the growth and differentiation of tumor specific CD4+ T helper and CD8+ T cytotoxic cells. Int J Cancer 45: 1096

    Google Scholar 

  30. Sylvan SP, Hellström UB (1989) Characterization of hepatitis B surface antigen (HBsAg) induced interleukin 2 secretion in chronic asymptomatic carriers of HBsAg. Clin Exp Immunol 78: 207

    Google Scholar 

  31. Sylvan SP, Hellström UB, Lundbergh PR (1985) Detection of cellular and humoral immunity to hepatitis B surface antigen (HBsAg) in asymptomatic HBsAg carriers. Clin Exp Immunol 62: 288

    Google Scholar 

  32. Van Riet I, Heirman C, Lacor P, De Waele M, Thielemans K, Van Camp B (1989) Detection of monoclonal B lymphocytes in bone marrow and peripheral blood of multiple myeloma patients by immunoglobulin gene rearrangement studies. Br J Haematol 73: 289

    Google Scholar 

  33. Waters SJ, Bona CA (1988) Characterization of a T cell clone recognizing idiotypes as tumor-associated antigens. Cell Immunol 111: 87

    Google Scholar 

  34. Wen T, Mellstedt H, Jondal M (1990) Presence of clonal T cell populations in chronic B lymphocytic leukemia and smoldering myeloma. J Exp Med 171: 659

    Google Scholar 

  35. Wilson A, George AJT, King CA, Stevenson FK (1990) Recognition of a B cell lymphoma by anti-idiotypic T cells. J Immunol 145: 3937

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Österborg, A., Masucci, M., Bergenbrant, S. et al. Generation of T cell clones binding F(ab′)2 fragments of the idiotypic immunoglobulin in patients with monoclonal gammopathy. Cancer Immunol Immunother 34, 157–162 (1991). https://doi.org/10.1007/BF01742306

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01742306

Key words

Navigation