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. 1973 Aug;52(8):1908–1917. doi: 10.1172/JCI107374

Impaired Lymphocyte Transformation in Hodgkin's Disease. EVIDENCE FOR DEPLETION OF CIRCULATING T-LYMPHOCYTES

Kenneth M Matchett 1, Andrew T Huang 1, William B Kremer 1
PMCID: PMC302472  PMID: 4541673

Abstract

The kinetics of lymphocyte transformation induced by phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were studied daily, with blood lymphocytes from normal individuals and from untreated patients in all stages of Hodgkin's disease (HD). In addition, spleen lymphocytes and lymph node lymphocytes were studied with similar techniques.

Peripheral blood lymphocyte transformation stimulated by PHA was found to be depressed in all patients with HD (including those with localized disease and no symptoms) when small numbers of lymphocytes were cultured and studied during a 7-day period. Most patients with HD had an increased number of cells circulating in their blood which were actively synthesizing DNA. HD lymphocytes which demonstrated the highest initial rate of spontaneous DNA synthesis usually did not respond to PHA stimulation.

Blood lymphocytes from normal individuals responded equally well to PHA and PWM in our system. HD blood lymphocytes consistently responded better to PWM than to PHA, with the response to PWM frequently within the normal range. Unless the spleen was extensively infiltrated with HD, spleen lymphocytes from patients with HD responded to PHA, even though the blood lymphocyte response was severely reduced. Lymph node lymphocyte response to PHA from patients with HD was variable, but correlated roughly with the blood lymphocyte response.

It is hypothesized from the data presented that in HD, circulating thymus-dependent (T-)lymphocytes are stimulated by the presence of active disease. This stimulation of T-lymphocytes leads to a circulating T-cell depletion and to an increase in the number of cells circulating that are active in DNA synthesis. The degree of impairment of cell-mediated immunity would then depend upon the degree of T-lymphocyte depletion.

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Selected References

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  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. Abdou N. I., Abdou N. L. Bone marrow: the bursa equivalent in man? Science. 1972 Jan 28;175(4020):446–448. doi: 10.1126/science.175.4020.446. [DOI] [PubMed] [Google Scholar]
  3. Bach M. L., Bach F. H., Widmer M., Oranen H., Wolberg W. H. Lymphocyte reactivity in vitro. VII. The effect of polymorphonuclear leukocytes on lymphocyte response. Transplantation. 1971 Oct;12(4):283–286. [PubMed] [Google Scholar]
  4. Bain B., Pshyk K. Enhanced reactivity in mixed leukocyte cultures after separation of mononuclear cells on Ficoll-Hypaque. Transplant Proc. 1972 Jun;4(2):163–164. [PubMed] [Google Scholar]
  5. Brown R. S., Haynes H. A., Foley H. T., Godwin H. A., Berard C. W., Carbone P. P. Hodgkin's disease. Immunologic, clinical, and histologic features of 50 untreated patients. Ann Intern Med. 1967 Aug;67(2):291–302. doi: 10.7326/0003-4819-67-2-291. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Corder M. P., Young R. C., Brown R. S., DeVita V. T. Phytohemagglutinin-induced lymphocyte transformation: the relationship to prognosis of Hodgkin's disease. Blood. 1972 May;39(5):595–601. [PubMed] [Google Scholar]
  9. Cowther D., Fairley G. H., Sewell R. L. Significance of the changes in the circulating lymphoid cells in Hodgkin's disease. Br Med J. 1969 May 24;2(5655):473–477. doi: 10.1136/bmj.2.5655.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Crowther D., Fairley G. H., Sewell R. L. Lymphoid cells in Hodgkin's disease. Nature. 1967 Sep 2;215(5105):1086–1088. doi: 10.1038/2151086a0. [DOI] [PubMed] [Google Scholar]
  11. Daniels J. C., Sakai H., Remmers A. R., Jr, Sarles H. E., Fish J. C., Cobb E. K., Levin W. C., Ritzmann S. E. In vitro reactivity of human lymphocytes in chronic uraemia: analysis and interpretation. Clin Exp Immunol. 1971 Feb;8(2):213–227. [PMC free article] [PubMed] [Google Scholar]
  12. Davies A. J., Leuchars E., Wallis V., Doenhoff M. J. A system for lymphocytes in the mouse. Proc R Soc Lond B Biol Sci. 1971 Jan 12;176(1045):369–384. doi: 10.1098/rspb.1971.0001. [DOI] [PubMed] [Google Scholar]
  13. Doenhoff M. J., Davies A. J., Leuchars E., Wallis V. The thymus and circulating lymphocytes of mice. Proc R Soc Lond B Biol Sci. 1970 Oct 13;176(1042):69–85. doi: 10.1098/rspb.1970.0035. [DOI] [PubMed] [Google Scholar]
  14. Goldman J. M., Hobbs J. R. The immunoglobulins in Hodgkin's disease. Immunology. 1967 Oct;13(4):421–431. [PMC free article] [PubMed] [Google Scholar]
  15. Gotoff S. P. Lymphocytes in congenital immunological deficiency diseases. Clin Exp Immunol. 1968 Oct;3(8):843–856. [PMC free article] [PubMed] [Google Scholar]
  16. Greaves M. F., Roitt I. M., Rose M. E. Effect of bursectomy and thymectomy on the responses of chicken peripheral blood lymphocytes to phytohaemagglutinin. Nature. 1968 Oct 19;220(5164):293–295. doi: 10.1038/220293a0. [DOI] [PubMed] [Google Scholar]
  17. HOFFMANN G. T., ROTTINO A. Studies of immunologic reactions of patients with Hodgkin's disease; antibody reaction to typhoid immunization. AMA Arch Intern Med. 1950 Dec;86(6):872–876. doi: 10.1001/archinte.1950.00230180077006. [DOI] [PubMed] [Google Scholar]
  18. Han T. Effect of sera from patients with Hodgkin's disease on normal lymphocyte response to phytohemagglutinin. Cancer. 1972 Jun;29(6):1626–1631. doi: 10.1002/1097-0142(197206)29:6<1626::aid-cncr2820290629>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Harris G., Littleton R. J. The effects of antigens and of phytohemagglutinin on rabbit spleen cell suspensions. J Exp Med. 1966 Oct 1;124(4):621–634. doi: 10.1084/jem.124.4.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Havemann K., Rubin A. D. The delayed response of c0ronic lymphocytic leukemia lymphocytes to phytohemagglutinin in vitro. Proc Soc Exp Biol Med. 1968 Mar;127(3):668–671. doi: 10.3181/00379727-127-32769. [DOI] [PubMed] [Google Scholar]
  22. Hersh E. M., Butler W. T., Rossen R. D., Morgan R. O., Suki W. In vitro studies of the human response to organ allografts: appearance and detection of circulating activation lymphocytes. J Immunol. 1971 Aug;107(2):571–578. [PubMed] [Google Scholar]
  23. Hersh E. M., Irvin W. S. Blastogenic responses of lymphocytes from patients with untreated and treated lymphomas. Lymphology. 1969 Dec;2(4):150–160. [PubMed] [Google Scholar]
  24. 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]
  25. Holm G., Perlmann P., Johansson B. Impaired phytohaemagglutinin-induced cytotoxicity in vitro of lymphocytes from patients with Hodgkin's disease or chronic lymphatic leukaemia. Clin Exp Immunol. 1967 May;2(3):351–360. [PMC free article] [PubMed] [Google Scholar]
  26. Jackson S. M., Garrett J. V., Craig A. W. Lymphocyte transformation changes during the clinical course of Hodgkin's disease. Cancer. 1970 Apr;25(4):843–850. doi: 10.1002/1097-0142(197004)25:4<843::aid-cncr2820250413>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  27. Janossy G., Greaves M. F. Lymphocyte activation. I. Response of T and B lymphocytes to phytomitogens. Clin Exp Immunol. 1971 Oct;9(4):483–498. [PMC free article] [PubMed] [Google Scholar]
  28. Janossy G., Greaves M. F. Lymphocyte activation. II. discriminating stimulation of lymphocyte subpopulations by phytomitogens and heterologous antilymphocyte sera. Clin Exp Immunol. 1972 Mar;10(3):525–536. [PMC free article] [PubMed] [Google Scholar]
  29. KELLY W. D., GOOD R. A., VARCO R. L. Anergy and skin homograft survival in Hodgkin's disease. Surg Gynecol Obstet. 1958 Nov;107(5):565–570. [PubMed] [Google Scholar]
  30. Mardiney M. R., Jr, Bock G. N., Chess L. The role of the human granulocyte as an antigen in the mixed lymphocyte reaction: the lack of stimulation. Transplantation. 1972 Aug;14(2):274–278. doi: 10.1097/00007890-197208000-00023. [DOI] [PubMed] [Google Scholar]
  31. Meuwissen H. J., Stutman O., Good R. A. Functions of the lymphocytes. Semin Hematol. 1969 Jan;6(1):28–66. [PubMed] [Google Scholar]
  32. Order S. E., Hellman S. Pathogenesis of Hodgkin's disease. Lancet. 1972 Mar 11;1(7750):571–573. doi: 10.1016/s0140-6736(72)90360-1. [DOI] [PubMed] [Google Scholar]
  33. Order S. E., Porter M., Hellman S. Hodgkin's disease: evidence for a tumor-associated antigen. N Engl J Med. 1971 Aug 26;285(9):471–474. doi: 10.1056/NEJM197108262850901. [DOI] [PubMed] [Google Scholar]
  34. Papac R. J. Lymphocyte transformation in malignant lymphomas. Cancer. 1970 Aug;26(2):279–286. doi: 10.1002/1097-0142(197008)26:2<279::aid-cncr2820260206>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  35. Roitt I. M., Greaves M. F., Torrigiani G., Brostoff J., Playfair J. H. The cellular basis of immunological responses. A synthesis of some current views. Lancet. 1969 Aug 16;2(7616):367–371. doi: 10.1016/s0140-6736(69)92712-3. [DOI] [PubMed] [Google Scholar]
  36. SCHIER W. W. Cutaneous anergy and Hodgkin's disease. N Engl J Med. 1954 Mar 4;250(9):353–361. doi: 10.1056/NEJM195403042500902. [DOI] [PubMed] [Google Scholar]
  37. SCHIER W. W., ROTH A., OSTROFF G., SCHRIFT M. H. Hodgkin's disease and immunity. Am J Med. 1956 Jan;20(1):94–99. doi: 10.1016/0002-9343(56)90176-0. [DOI] [PubMed] [Google Scholar]
  38. Shortman K., Byrd W. J., Cerottini J. C., Brunner K. T. Characterisation and separation of mouse lymphocyte subpopulations responding to phytohemagglutinin and pokeweed mitogens. Cell Immunol. 1973 Jan;6(1):25–40. doi: 10.1016/0008-8749(73)90003-8. [DOI] [PubMed] [Google Scholar]
  39. Silveira N. P., Mendes N. F., Tolnai M. E. Tissue localization of two populations of human lymphocytes distinguished by membrane receptors. J Immunol. 1972 May;108(5):1456–1460. [PubMed] [Google Scholar]
  40. Stockman G. D., Gallagher M. T., Heim L. R., South M. A., Trentin J. J. Differential stimulation of mouse lymphoid cells by phytohemagglutinin and pokeweed mitogen. Proc Soc Exp Biol Med. 1971 Mar;136(3):980–982. doi: 10.3181/00379727-136-35410. [DOI] [PubMed] [Google Scholar]
  41. Thomas J. W., Boldt W., Horrocks G., Low B. Lymphocyte transformation by phytohemagglutinin. I. In Hodgkin's Disease. Can Med Assoc J. 1967 Sep 30;97(14):832–836. [PMC free article] [PubMed] [Google Scholar]
  42. Trubowitz S., Masek B., Del Rosario A. Lymphocyte response to phytohemagglutinin in Hodgkin's disease, lymphatic leukemia and lymphosarcoma. Cancer. 1966 Dec;19(12):2019–2023. doi: 10.1002/1097-0142(196612)19:12<2019::aid-cncr2820191228>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  43. WALKER R. I., FOWLER I. GRANULOCYTE INHIBITION OF HUMAN PERIPHERAL BLOOD LYMPHOCYTE GROWTH IN VITRO. Exp Cell Res. 1965 May;38:379–385. doi: 10.1016/0014-4827(65)90411-8. [DOI] [PubMed] [Google Scholar]
  44. Wybran J., Chantler S., Fudenberg H. H. Isolation of normal T cells in chronic lymphatic leukaemia. Lancet. 1973 Jan 20;1(7795):126–129. doi: 10.1016/s0140-6736(73)90196-7. [DOI] [PubMed] [Google Scholar]
  45. 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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