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. 1980 Jul;66(1):141–148. doi: 10.1172/JCI109827

Depressed primary in vitro antibody response in untreated systemic lupus erythematosus. T helper cell defect and lack of defective suppressor cell function.

J F Delfraissy, P Segond, P Galanaud, C Wallon, P Massias, J Dormont
PMCID: PMC371515  PMID: 6447163

Abstract

The in vitro antibody response of peripheral blood lymphocytes (PBL) from 19 patients with untreated systemic lupus erythematosus (SLE) was compared with that of 20 control patients and 44 normal subjects. Trinitrophenyl polyacrylamide beads (TNP-PAA) were used to induce IgM anti-TNP plaque-forming cells. SLE patients displayed a markedly depressed, and in most instances virtually absent, response. This was not due to an unusual kinetics of the response; nor could it be induced by preincubation of SLE patients' PBL. In co-cultures of SLE patients and normal PBL, the former, with few exceptions, did not exert a suppressive effect. In four patients the anti-TNP response of either unfractionated or T-depleted SLE PBL could be restored by T cells from a normal individual. Conversely in three of these patients, SLE T cells could not support the response of normal B cells, suggesting a T helper cell defect in SLE PBL. Concanavalin A (Con A)-induced suppressor cells of the antibody response could be assayed by two approaches: (a) in responder SLE patients, by the direct addition of Con A to TNP-PAA-stimulated cultures; (b) in seven patients by transfer of Con A-activated cells to the responding culture of a normal allogeneic donor. In both cases SLE PBL were able to exert a suppressive effect to the same extent as normal PBL.

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Selected References

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

  1. Alarcón-Segovia D., Ruíz-Argüelles A. Decreased circulating thymus-derived cells with receptors for the Fc portion of immunoglobulin G in systemic lupus erythematosus. J Clin Invest. 1978 Dec;62(6):1390–1394. doi: 10.1172/JCI109260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Antel J. P., Arnason B. G. Suppressor cell function in man: evidence for altered sensitivity of responder cells with age. Clin Immunol Immunopathol. 1979 Jun;13(2):119–124. doi: 10.1016/0090-1229(79)90055-2. [DOI] [PubMed] [Google Scholar]
  3. Bach J. F. Evaluation of T-cells and thymic serum factors in man using the rosette technique. Transplant Rev. 1973;16(0):196–217. doi: 10.1111/j.1600-065x.1973.tb00121.x. [DOI] [PubMed] [Google Scholar]
  4. Baum J., Ziff M. Decreased 19S antibody response to bacterial antigens in systemic lupus erythematosus. J Clin Invest. 1969 Apr;48(4):758–767. doi: 10.1172/JCI106033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bobrove A. M., Miller P. Depressed in vitro B-lymphocyte differentiation in systemic lupus erythematosus. Arthritis Rheum. 1977 Sep-Oct;20(7):1326–1333. doi: 10.1002/art.1780200705. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Budman D. R., Merchant E. B., Steinberg A. D., Doft B., Gershwin M. E., Lizzio E., Reeves J. P. Increased spontaneous activity of antibody-forming cells in the peripheral blood of patients with active SLE. Arthritis Rheum. 1977 Apr;20(3):829–833. doi: 10.1002/art.1780200312. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Chiorazzi N., Fu S. M., Kunkel H. G. Induction of human antibody responses in vitro with emphasis on allogeneic helper factors. Immunol Rev. 1979;45:219–241. doi: 10.1111/j.1600-065x.1979.tb00279.x. [DOI] [PubMed] [Google Scholar]
  10. Cohen P. L., Ziff M. Abnormal polyclonal B cell activation in NZB/NZW F1 mice. J Immunol. 1977 Oct;119(4):1534–1537. [PubMed] [Google Scholar]
  11. Delfraissy J. F., Galanaud P., Dormont J., Wallon C. Age-related impairment of the in vitro antibody response in the human. Clin Exp Immunol. 1980 Jan;39(1):208–214. [PMC free article] [PubMed] [Google Scholar]
  12. Delfraissy J. F., Galanaud P., Dormont J., Wallon C. Primary in vitro antibody response from human peripheral blood lymphocytes. J Immunol. 1977 Feb;118(2):630–635. [PubMed] [Google Scholar]
  13. Delfraissy J. F., Galanaud P., Dormont J., Wallon C. Primary in vitro antibody response of human peripheral blood lymphocytes: role of phagocytic mononuclear cells. J Immunol. 1978 Apr;120(4):1283–1288. [PubMed] [Google Scholar]
  14. Fauci A. S., Steinberg A. D., Haynes B. F., Whalen G. Immunoregulatory aberrations in systemic lupus erythematosus. J Immunol. 1978 Oct;121(4):1473–1479. [PubMed] [Google Scholar]
  15. Galanaud P., Crevon M. C., Delfraissy J. F., Segond P., Wallon C., Dormont J. Regulation of the primary in vitro antibody response in human peripheral blood lymphocytes: different effects of mitogen-induced and spontaneous T suppressor cells. Clin Exp Immunol. 1979 Oct;38(1):106–115. [PMC free article] [PubMed] [Google Scholar]
  16. Galanaud P., Crevon M. C., Guenounou M., Agneray J., Dormont J. Sodium periodate-induced suppressor T cells of the human in vitro antibody response. Cell Immunol. 1980 Apr;51(1):85–91. doi: 10.1016/0008-8749(80)90240-3. [DOI] [PubMed] [Google Scholar]
  17. Galanaud P. In vitro antibody response to trinitrophenyl-polyacrylamide beads. Immunol Rev. 1979;45:141–161. doi: 10.1111/j.1600-065x.1979.tb00276.x. [DOI] [PubMed] [Google Scholar]
  18. Ginsburg W. W., Finkelman F. D., Lipsky P. E. Circulating and pokeweed mitogen-induced immunoglobulin-secreting cells in systemic lupus erythematosus. Clin Exp Immunol. 1979 Jan;35(1):76–88. [PMC free article] [PubMed] [Google Scholar]
  19. Gottlieb A. B., Lahita R. G., Chiorazzi N., Kunkel H. G. Immune function in systemic lupus erythematosus. Impairment of in vitro T-cell proliferation and in vivo antibody response to exogenous antigen. J Clin Invest. 1979 May;63(5):885–892. doi: 10.1172/JCI109388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Haynes B. F., Fauci A. S. Activation of human B lymphocytes. V. Kinetics and mechanisms of suppression of plaque-forming cell responses by concanavalin A-generated suppressor cells. J Immunol. 1978 Mar;120(3):700–708. [PubMed] [Google Scholar]
  21. Haynes B. F., Fauci A. S. Activation of human B lymphocytes. X. Heterogeneity of concanavalin A-generated suppressor cells of the pokeweed mitogen-induced plaque-forming cell response of human peripheral blood lymphocytes. J Immunol. 1978 Aug;121(2):559–565. [PubMed] [Google Scholar]
  22. Haynes B. F., Katz P., Fauci A. S. Mechanisms of corticosteroid action on lymphocyte subpopulations. V. Effects of in vivo hydrocortisone on the circulatory kinetics and function of naturally occuring and mitogen-induced suppressor cells in man. Cell Immunol. 1979 Apr;44(1):169–178. doi: 10.1016/0008-8749(79)90037-6. [DOI] [PubMed] [Google Scholar]
  23. Hayward A. R., Layward L., Lydyard P. M., Moretta L., Dagg M., Lawton A. R. Fc-receptor heterogeneity of human suppressor T cells. J Immunol. 1978 Jul;121(1):1–5. [PubMed] [Google Scholar]
  24. Horowitz S., Borcherding W., Moorthy A. V., Chesney R., Schulte-Wisserman H., Hong R. Induction of suppressor T cells in systemic lupus erythematosus by thymosin and cultured thymic epithelium. Science. 1977 Sep 2;197(4307):999–1001. doi: 10.1126/science.302032. [DOI] [PubMed] [Google Scholar]
  25. Horwitz D. A., Garrett M. A., Craig A. H. Serum effects of mitogenic reactivity in subjects with systemic lupus erythematosus, rheumatoid arthritis and scleroderma. Technical considerations and lack of correlation with anti-lymphocyte antibodies. Clin Exp Immunol. 1977 Jan;27(1):100–110. [PMC free article] [PubMed] [Google Scholar]
  26. Jackson C. G., Ochs H. D., Wedgwood R. J. Immune response of a patient with deficiency of the fourth component of complement and systemic lupus erythematosus. N Engl J Med. 1979 May 17;300(20):1124–1129. doi: 10.1056/NEJM197905173002002. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Kishimoto S., Tomino S., Inomata K., Kotegawa S., Saito T., Kuroki M., Mitsuya H., Hisamitsu S. Age-related changes in the subsets and functions of human T lymphocytes. J Immunol. 1978 Nov;121(5):1773–1780. [PubMed] [Google Scholar]
  29. Krakauer R. S., Clough J. D., Frank S., Sundeen J. T. Suppressor cell function defect in idiopathic systemic lupus erythematosus. Clin Immunol Immunopathol. 1979 Nov;14(3):327–333. doi: 10.1016/0090-1229(79)90158-2. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Miller K. B., Schwartz R. S. Familial abnormalities of suppressor-cell function in systemic lupus erythematosus. N Engl J Med. 1979 Oct 11;301(15):803–809. doi: 10.1056/NEJM197910113011502. [DOI] [PubMed] [Google Scholar]
  32. Moretta L., Mingari M. C., Moretta A. Hunan T cell subpopulations in normal and pathologic conditions. Immunol Rev. 1979;45:163–193. doi: 10.1111/j.1600-065x.1979.tb00277.x. [DOI] [PubMed] [Google Scholar]
  33. Morimoto C., Abe T., Hara M., Homma M. In vitro TNP-specific antibody formation by peripheral lymphocytes from patients with systemic lupus erythematosus. Scand J Immunol. 1977;6(6-7):575–579. doi: 10.1111/j.1365-3083.1977.tb02135.x. [DOI] [PubMed] [Google Scholar]
  34. Morimoto C., Abe T., Homma M. Altered function of suppressor T lymphocytes in patients with active systemic lupus erythematosus--in vitro immune response to autoantigen. Clin Immunol Immunopathol. 1979 Jun;13(2):161–170. doi: 10.1016/0090-1229(79)90060-6. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Newman B., Blank S., Lomnitzer R., Disler P., Rabson A. R. Lack of suppressor cell activity in systemic lupus erythematosus. Clin Immunol Immunopathol. 1979 Jun;13(2):187–193. doi: 10.1016/0090-1229(79)90063-1. [DOI] [PubMed] [Google Scholar]
  37. Nies K. M., Louie J. S. Impaired immunoglobulin synthesis by peripheral blood lymphocytes in systemic lupus erythematosus. Arthritis Rheum. 1978 Jan-Feb;21(1):51–57. doi: 10.1002/art.1780210109. [DOI] [PubMed] [Google Scholar]
  38. Pincus T., Schur P. H., Rose J. A., Decker J. L., Talal N. Measurement of serum DNA-binding activity in systemic lupus erythematosus. N Engl J Med. 1969 Sep 25;281(13):701–705. doi: 10.1056/NEJM196909252811304. [DOI] [PubMed] [Google Scholar]
  39. Primi D., Hammarström L., Smith C. I. Genetic control of lymphocyte suppression. I. Lack of suppression in aged NZB mice is due to a B cell defect. J Immunol. 1978 Dec;121(6):2241–2243. [PubMed] [Google Scholar]
  40. Roder J. C., Bell D. A., Singhal S. K. Regulation of the immune response in autoimmune NZB/NZW F1 mice. I. The spontaneous generation of splenic suppressor cells. Cell Immunol. 1977 Mar 15;29(2):272–284. doi: 10.1016/0008-8749(77)90322-7. [DOI] [PubMed] [Google Scholar]
  41. Sakane T., Steinberg A. D., Green I. Failure of autologous mixed lymphocyte reactions between T and non-T cells in patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3464–3468. doi: 10.1073/pnas.75.7.3464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sakane T., Steinberg A. D., Reeves J. P., Green I. Studies of immune functions of patients with systemic lupus erythematosus. Complement-dependent immunoglobulin M anti-thymus-derived cell antibodies preferentially inactivate suppressor cells. J Clin Invest. 1979 May;63(5):954–965. doi: 10.1172/JCI109396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Saxon A., Stevens R. H., Ramer S. J., Clements P. J., Yu D. T. Glucocorticoids administered in vivo inhibit human suppressor T lymphocyte function and diminish B lymphocyte responsiveness in in vitro immunoglobulin synthesis. J Clin Invest. 1978 Apr;61(4):922–930. doi: 10.1172/JCI109017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Segond P., Delfraissy J. F., Galanaud P., Wallon C., Massias P., Dormont J. Depressed primary in vitro antibody response in rheumatoid arthritis. Clin Exp Immunol. 1979 Aug;37(2):196–204. [PMC free article] [PubMed] [Google Scholar]
  45. Tardieu M., Dupuy J. M. Suppressor activity of lymphocytes from patients with systemic lupus erythematosus. Clin Immunol Immunopathol. 1978 Oct;11(2):125–130. doi: 10.1016/0090-1229(78)90037-5. [DOI] [PubMed] [Google Scholar]
  46. Williams G. W., Steinberg A. D., Reinertsen J. L., Klassen L. W., Decker J. L., Dolin R. Influenza immunization in systemic lupus eruthematosus. A double-blind trial. Ann Intern Med. 1978 Jun;88(6):729–734. doi: 10.7326/0003-4819-88-6-729. [DOI] [PubMed] [Google Scholar]

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