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. 1975 Aug;56(2):467–475. doi: 10.1172/JCI108113

Hodgkin's disease. An immunodepleting and immunosuppressive disorder.

J J Twomey, A H Laughter, S Farrow, C C Douglass
PMCID: PMC436607  PMID: 125290

Abstract

Irradiated leukocytes or mononuclear leukocytes, from 16 out of 30 patients with Hodgkin's disease and from one patient with the Sézary syndrome, stimulated in culture subnormal (3H)thymidine incorporation by allogeneic lymphocytes from normal individuals. This abnormality was not demonstrated in any of 30 other patients with non-Hodgkin's lymphomas. Subnormal mixed leukocyte culture reaction activation was caused by suppression of the mixed leukocyte reaction by patients' cells. Inhibition of the reaction by patient mononuclear leukocytes was corrected when adherent cells were removed or when protein synthesis was inhibited with cycloheximide. The inhibitory cells were probably lymphocytes since selective removal of phagocytic cells did not remove the inhibition by other patient mononuclear leukocytes. The presence in culture of as few as 2,500 granulocytes per mm3 also reduced responses when target cells were from patients with Hodgkin's disease. Patient cells no longer suppressed the mixed leukocyte reaction after patients entered clinical remission which suggests that suppression is a reversible, disease-related abnormality. Thus, the immune deficiency with advance Hodgkin's disease caused by ly lymphocyte depletion may be compounded by a relative excess of suppressor lymphocytes. The overall immunodeficiency may be further compounded by suppression of immune response by granulocytes at even physiologic concentrations.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AISENBERG A. C. Studies on delayed hypersensitivity in Hodgkin's disease. J Clin Invest. 1962 Nov;41:1964–1970. doi: 10.1172/JCI104654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aisenberg A. C., Bloch K. J. Immunoglobulins on the surface of neoplastic lymphocytes. N Engl J Med. 1972 Aug 10;287(6):272–276. doi: 10.1056/NEJM197208102870603. [DOI] [PubMed] [Google Scholar]
  3. Arpels C., Southam C. M. Cytotoxicity of sera from healthy persons and cancer patients. Int J Cancer. 1969 Jul 15;4(4):548–559. doi: 10.1002/ijc.2910040419. [DOI] [PubMed] [Google Scholar]
  4. Bach F. H., Voynow N. K. One-way stimulation in mixed leukocyte cultures. Science. 1966 Jul 29;153(3735):545–547. doi: 10.1126/science.153.3735.545. [DOI] [PubMed] [Google Scholar]
  5. Barker A. D., Waksal S. D. Thymus-derived lymphocyte differentiation and lymphocytic leukemias. I. Evidence for the existence of functionally different subpopulations of thymus-derived cells in leukemic AKR mice. Cell Immunol. 1974 Apr;12(1):140–149. doi: 10.1016/0008-8749(74)90065-3. [DOI] [PubMed] [Google Scholar]
  6. Blaese R. M., Oppenheim J. J., Seeger R. C., Waldmann T. A. Lymphocyte-macrophage interaction in antigen induced in vitro lymphocyte transformation in patients with the Wiskott-Aldrich syndrome and other diseases with anergy. Cell Immunol. 1972 Jul;4(3):228–242. doi: 10.1016/0008-8749(72)90027-5. [DOI] [PubMed] [Google Scholar]
  7. Brody J. I. Augmentation of leukemic lymphocyte reactivity to phytohemagglutinin by salivary receptor. Blood. 1972 Jul;40(1):70–76. [PubMed] [Google Scholar]
  8. Brouet J. C., Flandrin G., Seligmann M. Indications of the thymus-derived nature of the proliferating cells in six patients with Sézary's syndrome. N Engl J Med. 1973 Aug 16;289(7):341–344. doi: 10.1056/NEJM197308162890703. [DOI] [PubMed] [Google Scholar]
  9. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  10. Casazza A. R., Duvall C. P., Carbone P. P. Infection in lymphoma. Histology, treatment, and duration in relation to incidence and survival. JAMA. 1966 Aug 29;197(9):710–716. doi: 10.1001/jama.197.9.710. [DOI] [PubMed] [Google Scholar]
  11. Ceppellini R., van Rood J. J. The HL-A system. I. Genetics and molecular biology. Semin Hematol. 1974 Jul;11(3):233–251. [PubMed] [Google Scholar]
  12. Chase M. W. Delayed-type hypersensitivity and the immunology of Hodgkin's disease, with a parallel examination of sarcoidosis. Cancer Res. 1966 Jun;26(6):1097–1120. [PubMed] [Google Scholar]
  13. Chess L., MacDermott R. P., Schlossman S. F. Immunologic functions of isolated human lymphocyte subpopulations. II. Antigen triggering of T and B cells in vitro. J Immunol. 1974 Oct;113(4):1122–1127. [PubMed] [Google Scholar]
  14. Douglas S. D., Goldberg L. S., Fudenberg H. H. Clinical, serologic and leukocyte function studies on patients with idiopathic "acquired" agammaglobulinemia and their families. Am J Med. 1970 Jan;48(1):48–53. doi: 10.1016/0002-9343(70)90097-5. [DOI] [PubMed] [Google Scholar]
  15. Dutton R. W. Inhibitory and stimulatory effects of concanavalin A on the response of mouse spleen cell suspensions to antigen. II. Evidence for separate stimulatory and inhibitory cells. J Exp Med. 1973 Dec 1;138(6):1496–1505. doi: 10.1084/jem.138.6.1496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Edelson R. L., Kirkpatrick C. H., Shevach E. M., Schein P. S., Smith R. W., Green I., Lutzner M. Preferential cutaneous infiltration by neoplastic thymus-derived lymphocytes. Morphologic and functional studies. Ann Intern Med. 1974 Jun;80(6):685–692. doi: 10.7326/0003-4819-80-6-685. [DOI] [PubMed] [Google Scholar]
  17. Folch H., Waksman B. H. The splenic suppressor cell. I. Activity of thymus-dependent adherent cells: changes with age and stress. J Immunol. 1974 Jul;113(1):127–139. [PubMed] [Google Scholar]
  18. Folch H., Waksman B. H. The splenic suppressor cell. II. Suppression of mixed lymphocyte reaction by thymus-dependent adherent cells. J Immunol. 1974 Jul;113(1):140–144. [PubMed] [Google Scholar]
  19. GROSS L. Biological and pathogenic properites of a mouse leukemia virus. Acta Haematol. 1960 May;23:259–275. doi: 10.1159/000206247. [DOI] [PubMed] [Google Scholar]
  20. Gaines J. D., Gilmer M. A., Remington J. S. Deficiency of lymphocyte antigen recognition in Hodgkin's disease. Natl Cancer Inst Monogr. 1973 May;36:117–121. [PubMed] [Google Scholar]
  21. Geha R. S., Schneeberger E., Merler E., Rosen F. S. Heterogeneity of "acquired" or common variable agammaglobulinemia. N Engl J Med. 1974 Jul 4;291(1):1–6. doi: 10.1056/NEJM197407042910101. [DOI] [PubMed] [Google Scholar]
  22. Gerber N. L., Hardin J. A., Chused T. M., Steinberg A. D. Loss with age in NZB-W mice of thymic suppressor cells in the graft-vs-host reaction. J Immunol. 1974 Nov;113(5):1618–1625. [PubMed] [Google Scholar]
  23. Gershon R. K. T cell control of antibody production. Contemp Top Immunobiol. 1974;3:1–40. doi: 10.1007/978-1-4684-3045-5_1. [DOI] [PubMed] [Google Scholar]
  24. Gotoff S. P., Lolekha S., Lopata M., Kopp J., Kopp R. L., Malecki T. J. The macrophage aggregation assay for cell-mediated immunity in man. Studies of patients with Hodgkin's disease and sarcoidosis. J Lab Clin Med. 1973 Oct;82(4):682–691. [PubMed] [Google Scholar]
  25. Han T., Sokal J. E. Lymphocyte response to phytohemagglutinin in Hodgkin's disease. Am J Med. 1970 Jun;48(6):728–734. doi: 10.1016/s0002-9343(70)80008-0. [DOI] [PubMed] [Google Scholar]
  26. Heiss L. I., Palmer D. L. Anergy in patients with leukocytosis. Am J Med. 1974 Mar;56(3):323–332. doi: 10.1016/0002-9343(74)90614-7. [DOI] [PubMed] [Google Scholar]
  27. Hersh E. M., Oppenheim J. J. Impaired in vitro lymphocyte transformation in Hodgkin's disease. N Engl J Med. 1965 Nov 4;273(19):1006–1012. doi: 10.1056/NEJM196511042731903. [DOI] [PubMed] [Google Scholar]
  28. Kappler J. W., Hunter P. C., Jacobs D., Lord E. Functional heterogeneity among the T-derived lymphocytes of the mouse. I. Analysis by adult thymectomy. J Immunol. 1974 Jul;113(1):27–38. [PubMed] [Google Scholar]
  29. Levy R., Kaplan H. S. Impaired lymphocyte function in untreated Hodgkin's disease. N Engl J Med. 1974 Jan 24;290(4):181–186. doi: 10.1056/NEJM197401242900402. [DOI] [PubMed] [Google Scholar]
  30. Lukes R. J., Butler J. J. The pathology and nomenclature of Hodgkin's disease. Cancer Res. 1966 Jun;26(6):1063–1083. [PubMed] [Google Scholar]
  31. Matchett K. M., Huang A. T., Kremer W. B. Impaired lymphocyte transformation in Hodgkin's disease. Evidence for depletion of circulating t-lymphocytes. J Clin Invest. 1973 Aug;52(8):1908–1917. doi: 10.1172/JCI107374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mittal K. K., Mickey M. R., Singal D. P., Terasaki P. I. Serotyping for homotransplantation. 18. Refinement of microdroplet lymphocyte cytotoxicity test. Transplantation. 1968 Nov;6(8):913–927. doi: 10.1097/00007890-196811000-00006. [DOI] [PubMed] [Google Scholar]
  33. Nelson D. S. Production by stimulated macrophages of factors depressing lymphocyte transformation. Nature. 1973 Nov 30;246(5431):306–307. doi: 10.1038/246306a0. [DOI] [PubMed] [Google Scholar]
  34. Peter C. R., MacKenzie M. R., Glassy F. J. T or B cell origin of some non-Hodgkin's lymphomas. Lancet. 1974 Sep 21;2(7882):686–689. doi: 10.1016/s0140-6736(74)93263-2. [DOI] [PubMed] [Google Scholar]
  35. Preud'homme J. L., Seligmann M. Surface bound immunoglobulins as a cell marker in human lymphoproliferative diseases. Blood. 1972 Dec;40(6):777–794. [PubMed] [Google Scholar]
  36. Rabellino E., Colon S., Grey H. M., Unanue E. R. Immunoglobulins on the surface of lymphocytes. I. Distribution and quantitation. J Exp Med. 1971 Jan 1;133(1):156–167. doi: 10.1084/jem.133.1.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rodey G. E., Sprader J. C., Bortin M. M. Inhibition of normal allogeneic responder cells in mouse mixed leukocyte culture by long-passage AKR leukemic lymphoblasts. Cancer Res. 1974 Jun;34(6):1289–1294. [PubMed] [Google Scholar]
  38. Seligmann M., Brouet J. C. Antibody activity of human myeloma globulins. Semin Hematol. 1973 Apr;10(2):163–177. [PubMed] [Google Scholar]
  39. Smith J. L., Cowling D. C., Barker C. R. Response of lymphocytes in chronic lymphocytic leukaemia to plant mitogens. Lancet. 1972 Jan 29;1(7744):229–233. doi: 10.1016/s0140-6736(72)90624-1. [DOI] [PubMed] [Google Scholar]
  40. Twomey J. J., Douglass C. C. An in vitro study of lymphocyte and macrophage function with lymphoproliferative neoplasms. Cancer. 1974 Apr;33(4):1034–1038. doi: 10.1002/1097-0142(197404)33:4<1034::aid-cncr2820330420>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  41. Twomey J. J., Douglass C. C., Morris S. M. Inability of leukocytes to stimulate mixed leukocyte reactions. J Natl Cancer Inst. 1973 Aug;51(2):345–351. [PubMed] [Google Scholar]
  42. Twomey J. J., Sharkey O. An adaptation of the mixed leukocyte culture test for use in evaluating lymphocyte and macrophage function. J Immunol. 1972 Apr;108(4):984–990. [PubMed] [Google Scholar]
  43. Twomey J. J., Sharkey O., Jr, Brown J. A., Laughter A. H., Jordan P. H., Jr Cellular requirements for the mitotic response in allogeneic mixed leukocyte cultures. J Immunol. 1970 Apr;104(4):845–853. [PubMed] [Google Scholar]
  44. Waldmann T. A., Durm M., Broder S., Blackman M., Blaese R. M., Strober W. Role of suppressor T cells in pathogenesis of common variable hypogammaglobulinaemia. Lancet. 1974 Sep 14;2(7881):609–613. doi: 10.1016/s0140-6736(74)91940-0. [DOI] [PubMed] [Google Scholar]
  45. Weiner M. S., Bianco C., Nussenzweig V. Enhanced binding of neuraminidase-treated sheep erythrocytes to human T lymphocytes. Blood. 1973 Dec;42(6):939–946. [PubMed] [Google Scholar]
  46. Wernet P., Kunkel H. G. Antibodies to a specific surface antigen of T cells in human sera inhibiting mixed leukocyte culture reactions. J Exp Med. 1973 Oct 1;138(4):1021–1026. doi: 10.1084/jem.138.4.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Woodruff J. J., Gesner B. M. The effect of neuraminidase on the fate of transfused lymphocytes. J Exp Med. 1969 Mar 1;129(3):551–567. doi: 10.1084/jem.129.3.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Young R. C., Corder M. P., Haynes H. A., DeVita V. T. Delayed hypersensitivity in Hodgkin's disease. A study of 103 untreated patients. Am J Med. 1972 Jan;52(1):63–72. doi: 10.1016/0002-9343(72)90008-3. [DOI] [PubMed] [Google Scholar]

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