Generation of T cell clones binding F(ab′)2 fragments of the idiotypic immunoglobulin in patients with monoclonal gammopathy
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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.
Key words
Monoclonal gammopathy Idiotype T cellsPreview
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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: 1635Google 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: 728Google 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: 1550Google 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: 66Google 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: 411Google Scholar
- 6.Böyum A (1983) Isolation of human blood monocytes with Nycodenz, a new non-ionic iodinated gradient medium. Scand J Immunol 17: 429Google 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: 3718Google Scholar
- 8.Daley MJ, Gebel HM, Lynch RG (1978) Idiotype-specific transplantation resistance to MOPC-315: abrogation by post-immunization thymectomy. J Immunol 120: 1620Google 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: 1064Google Scholar
- 10.Durie BGM, Salmon SE (1975) A clinical staging system for multiple myeloma. Cancer 36: 842Google 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: 424Google 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 151Google 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: 253Google Scholar
- 14.Grey HM, Sette A, Buus S (1989) How T cells see antigen. Sci Am 261: 38Google 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: 1776Google Scholar
- 16.Jerne NK (1974) Towards a network theory of the immune system. Ann Immunol (Paris) 125C: 373Google Scholar
- 17.Jörgensen T, Hannestad K (1982) Helper T recognition of the variable domains of a mouse myeloma protein (315). J Exp Med 155: 1587Google Scholar
- 18.Lynch RG (1987) Immunoglobulin-specific suppressor T cells. Adv Immunol 40: 135Google 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: 1540Google 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: 45Google Scholar
- 21.Mellstedt H, Björkholm M, Holm G (1977) Intermittent melphalan prednisone therapy in plasma cell myeloma. Acta Med Scand 202: 5Google 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: 257Google 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: 852Google Scholar
- 24.Milburn GL, Lynch RG (1983) Anti-idiotypic regulation of IgA expression in myeloma cells. Mol Immunol 20: 931Google 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: 227Google Scholar
- 26.Pettersson D, Mellstedt H, Holm G (1978) IgG on human blood lymphocytes studied by immunofluorescence. Scand J Immunol 8: 535Google 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: 287Google 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: 1046Google 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: 1096Google 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: 207Google 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: 288Google 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: 289Google Scholar
- 33.Waters SJ, Bona CA (1988) Characterization of a T cell clone recognizing idiotypes as tumor-associated antigens. Cell Immunol 111: 87Google 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: 659Google 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: 3937Google Scholar