Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Oct;75(10):5150–5154. doi: 10.1073/pnas.75.10.5150

Direct evidence for loss of human suppressor cells during active autoimmune disease.

A J Strelkauskas, R T Callery, J McDowell, Y Borel, S F Schlossman
PMCID: PMC336282  PMID: 311007

Abstract

These studies indicate that a regulatory subset of lymphocytes is missing in patients with juvenile rheumatoid arthritis but these patients have antibodies in their serum that react with normal T cells. This regulatory subset of T cells is, however, present in patients whose serum shows little or no reactivity with normal T cells. In addition, patients who are deficient in this regulatory subset of lymphocytes significantly higher numbers of cells secreting Ig as measured by a hemolytic plaque assay. The significance of these observations is twofold: first, they represent a positive relationship among the loss of regulation overproduction of immunoglobulin, and the presence of anti-T cell antibodies and second and perhaps of equal importance, is the indication that serum from patients with autoimmune diseases may give us a readily available reagent with which to dissect further functionally distinct subsets of normal T cells in man.

Full text

PDF
5150

Selected References

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

  1. ANSELL B. M., BYWATERS E. G. Prognosis in Still's disease. Bull Rheum Dis. 1959 May;9(9):189–192. [PubMed] [Google Scholar]
  2. Bresnihan B., Jasin H. E. Suppressor function of peripheral blood mononuclear cells in normal individuals and in patients with systemic lupus erythematosus. J Clin Invest. 1977 Jan;59(1):106–116. doi: 10.1172/JCI108607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Broder S., Humphrey R., Durm M., Blackman M., Meade B., Goldman C., Strober W., Waldmann T. Impaired synthesis of polyclonal (non-paraprotein) immunoglobulins by circulating lymphocytes from patients with multiple myeloma Role of suppressor cells. N Engl J Med. 1975 Oct 30;293(18):887–892. doi: 10.1056/NEJM197510302931801. [DOI] [PubMed] [Google Scholar]
  4. Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cantor H., Boyse E. A. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med. 1975 Jun 1;141(6):1376–1389. doi: 10.1084/jem.141.6.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cantor H., Boyse E. A. Regulation of cellular and humoral immune responses by T-cell subclasses. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):23–32. doi: 10.1101/sqb.1977.041.01.006. [DOI] [PubMed] [Google Scholar]
  7. Cantor H., McVay-Boudreau L., Hugenberger J., Naidorf K., Shen F. W., Gershon R. K. Immunoregulatory circuits among T-cell sets. II. Physiologic role of feedback inhibition in vivo: absence in NZB mice. J Exp Med. 1978 Apr 1;147(4):1116–1125. doi: 10.1084/jem.147.4.1116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chess L., MacDermott R. P., Schlossman S. F. Immunologic functions of isolated human lymphocyte subpopulations. I. Quantitative isolation of human T and B cells and response to mitogens. J Immunol. 1974 Oct;113(4):1113–1121. [PubMed] [Google Scholar]
  9. Eardley D. D., Hugenberger J., McVay-Boudreau L., Shen F. W., Gershon R. K., Cantor H. Immunoregulatory circuits among T-cell sets. I. T-helper cells induce other T-cell sets to exert feedback inhibition. J Exp Med. 1978 Apr 1;147(4):1106–1115. doi: 10.1084/jem.147.4.1106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Engleman E. G., McMichael A. J., Batey M. E., McDevitt H. O. A suppressor T cell of the mixed lymphocyte reaction in man specific for the stimulating alloantigen. Evidence that identity at HLA-D between suppressor and responder is required for suppression. J Exp Med. 1978 Jan 1;147(1):137–146. doi: 10.1084/jem.147.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Evans R. L., Lazarus H., Penta A. C., Schlossman S. F. Two functionally distinct subpopulations of human T cells that collaborate in the generation of cytotoxic cells responsible for cell-mediated lympholysis. J Immunol. 1978 Apr;120(4):1423–1428. [PubMed] [Google Scholar]
  12. 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]
  13. Greene M. I., Dorf M. E., Pierres M., Benacerraf B. Reduction of syngeneic tumor growth by an anti-I-J-alloantiserum. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5118–5121. doi: 10.1073/pnas.74.11.5118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hara M., Morimoto C., Takahashi H., Abe T., Homma M. Peripheral blood T-lymphocytes during the course of systemic lupus erythematosus. Keio J Med. 1975 Dec;24(4):263–273. doi: 10.2302/kjm.24.263. [DOI] [PubMed] [Google Scholar]
  15. Huber B., Devinsky O., Gershon R. K., Cantor H. Cell-mediated immunity: delayed-type hypersensitivity and cytotoxic responses are mediated by different T-cell subclasses. J Exp Med. 1976 Jun 1;143(6):1534–1539. doi: 10.1084/jem.143.6.1534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jandinski J., Cantor H., Tadakuma T., Peavy D. L., Pierce C. W. Separation of helper T cells from suppressor T cells expressing different Ly components. I. Polyclonal activation: suppressor and helper activities are inherent properties of distinct T-cell subclasses. J Exp Med. 1976 Jun 1;143(6):1382–1390. doi: 10.1084/jem.143.6.1382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jasin H. E., Ziff M. Immunoglobulin synthesis by peripheral blood cells in systemic lupus erythematosus. Arthritis Rheum. 1975 May-Jun;18(3):219–228. doi: 10.1002/art.1780180305. [DOI] [PubMed] [Google Scholar]
  18. Klassen L. W., Krakauer R. S., Steinberg A. D. Selective loss of suppressor cell function in New Zealand mice induced by NTA. J Immunol. 1977 Sep;119(3):830–830. [PubMed] [Google Scholar]
  19. Krakauer R. S., Waldmann T. A., Strober W. Loss of suppressor T cells in adult NZB/NZW mice. J Exp Med. 1976 Sep 1;144(3):662–673. doi: 10.1084/jem.144.3.662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McMichael A. J., Sasazuki T. A suppressor T cell in the human mixed lymphocyte reaction. J Exp Med. 1977 Aug 1;146(2):368–380. doi: 10.1084/jem.146.2.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Molinaro G. A., Maron E., Dray S. Antigen-secreting cells: enumeration of immunoglobulin-allotype-secreting cells in nonimmunized rabbits by means of hybrid-antibody-coated erythrocytes in a reverse hemolytic plaque assay. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1229–1233. doi: 10.1073/pnas.71.4.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Moretta L., Ferrarini M., Mingari M. C., Moretta A., Webb S. R. Subpopulations of human T cells identified by receptors for immunoglobulins and mitogen responsiveness. J Immunol. 1976 Dec;117(6):2171–2174. [PubMed] [Google Scholar]
  23. Morimoto C. Loss of suppressor T-lymphocyte function in patients with systemic lupus erythematosus (SLE). Clin Exp Immunol. 1978 Apr;32(1):125–133. [PMC free article] [PubMed] [Google Scholar]
  24. Okumura K., Takemori T., Tokuhisa T., Tada T. Specific enrichment of the suppressor T cell bearing I-J determinants: parallel functional and serological characterizations. J Exp Med. 1977 Nov 1;146(5):1234–1245. doi: 10.1084/jem.146.5.1234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pierres M., Germain R. N., Dorf M. E., Benacerraf B. Potentiation of a primary in vivo antibody response by alloantisera against gene products of the I region of the H-2 complex. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3975–3979. doi: 10.1073/pnas.74.9.3975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Reinisch C. L., Andrew S. L., Schlossman S. F. Suppressor cell regulation of immune response to tumors: abrogation by adult thymectomy. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2989–2992. doi: 10.1073/pnas.74.7.2989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schlossman S. F., Chess L., Humphreys R. E., Strominger J. L. Distribution of Ia-like molecules on the surface of normal and leukemic human cells. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1288–1292. doi: 10.1073/pnas.73.4.1288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Shou L., Schwartz S. A., Good R. A. Suppressor cell activity after concanavalin A treatment of lymphocytes from normal donors. J Exp Med. 1976 May 1;143(5):1100–1110. doi: 10.1084/jem.143.5.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Strelkauskas A. J., Eby W. C., Molinaro G. A., Dray S. Assessment of a B-cell function in chronic lymphocytic leukemia. Clin Immunol Immunopathol. 1976 Nov;6(3):334–340. doi: 10.1016/0090-1229(76)90086-6. [DOI] [PubMed] [Google Scholar]
  30. Strelkauskas A. J., Schauf V., Wilson B. S., Chess L., Schlossman S. F. Isolation and characterization of naturally occurring subclasses of human peripheral blood T cells with regulatory functions. J Immunol. 1978 Apr;120(4):1278–1282. [PubMed] [Google Scholar]
  31. Strelkauskas A. J., Teodorescu M., Dray S. Enumeration and isolation of human T and B lymphocytes by rosette formation with antibody-coated erythrocytes. Clin Exp Immunol. 1975 Oct;22(1):62–71. [PMC free article] [PubMed] [Google Scholar]
  32. Strelkauskas A. J., Wilson B. S., Callery R. T., Chess L., Schlossman S. F. T-cell regulation of human peripheral blood B-cells responsiveness. J Exp Med. 1977 Dec 1;146(6):1765–1772. doi: 10.1084/jem.146.6.1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Talal N., Steinberg A. D. The pathogenesis of autoimmunity in New Zealand black mice. Curr Top Microbiol Immunol. 1974;64(0):79–103. doi: 10.1007/978-3-642-65848-8_3. [DOI] [PubMed] [Google Scholar]
  34. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES