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. 1983 May;71(5):1402–1409. doi: 10.1172/JCI110893

In vitro nucleoside specific immune response by lymphocytes from systemic lupus erythematosus.

C Morimoto, A D Steinberg, S F Schlossman, Y Borel
PMCID: PMC437004  PMID: 6189861

Abstract

The in vitro immune response of systemic lupus erythematosus (SLE) lymphocytes to nucleosides conjugated to keyhole limpet hemocyanin (KLH) (A,G,C,T-KLH) was investigated. The nucleosides were chosen not only because they are a part of nucleic acid antigen and involved in autoimmunity, but also because nucleoside covalently bound to either soluble IgG or cells had been shown to induce unresponsiveness in mice. A significant proliferation index was induced in SLE lymphocytes, as compared with normal or rheumatoid arthritis (RA) lymphocytes in vitro [in (A,G,C,T)-KLH, 1 microgram/ml; stimulation index = M +/- SE, SLE 2.10 +/- 0.26, RA 1.06 +/- 0.14, normal 1.12 +/- 0.12 P less than 0.05]. Lymphocytes from SLE patients responded specifically to low doses of (A,G,C,T)-KLH and not to the protein carrier KLH alone. A solid-phase radioimmunoassay was developed to detect nucleoside-specific antibody. SLE lymphocytes spontaneously produced high levels of anti-A,G,C,T antibody. This was further increased by antigenic stimulation, but not with pokeweed mitogen (PWM) stimulation. In contrast normal lymphocytes failed to produce anti-A,G,C,T antibody either spontaneously or in response to antigen. However, normal lymphocytes produced antibody after stimulation with PWM. More importantly, anti-A,G,C,T antibody production by SLE lymphocytes was suppressed by preincubation with A,G,C,T-IgG (A,G,C,T-HGG). The antigen-specific unresponsiveness caused by A,G,C,T-HGG was demonstrated by the observation that preincubation with A,G,C,T-HGG did not affect the production of anti-dinitrophenyl antibody response. The ability to manipulate the altered response of SLE lymphocytes to nucleic acid antigens may have therapeutic implications in these patients.

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Selected References

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

  1. Abdou N. I., Sagawa A., Pascual E., Hebert J., Sadeghee S. Suppressor T-cell abnormality in idiopathic systemic lupus erythematosus. Clin Immunol Immunopathol. 1976 Sep;6(2):192–199. doi: 10.1016/0090-1229(76)90110-0. [DOI] [PubMed] [Google Scholar]
  2. Abe T., Hara M., Yamasaki K., Homma M. Cell-mediated immune response in systemic lupus erythematosus. In vitro cellular response to native DNA by macrophage inhibitory test. Arthritis Rheum. 1973 Sep-Oct;16(5):688–694. doi: 10.1002/art.1780160514. [DOI] [PubMed] [Google Scholar]
  3. Bankhurst A. D., Williams R. C., Jr Identification of DNA-binding lymphocytes in patients with systemic lupus erythematosus. J Clin Invest. 1975 Dec;56(6):1378–1385. doi: 10.1172/JCI108218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Borel Y., Lewis R. M., Stollar B. D. Prevention of murine lupus nephritis by carrier-dependent induction of immunologic tolerance to denatured DNA. Science. 1973 Oct 5;182(4107):76–78. doi: 10.1126/science.182.4107.76. [DOI] [PubMed] [Google Scholar]
  6. Borel Y., Young M. C. Nucleic acid-specific suppressor T cells. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1593–1596. doi: 10.1073/pnas.77.3.1593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. ERLANGER B. F., BEISER S. M. ANTIBODIES SPECIFIC FOR RIBONUCLEOSIDES AND RIBONUCLEOTIDES AND THEIR REACTION WITH DNA. Proc Natl Acad Sci U S A. 1964 Jul;52:68–74. doi: 10.1073/pnas.52.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eshhar Z., Benacerraf B., Katz D. H. Induction of tolerance to nucleic acid determinants by administration of a complex of nucleoside D-glutamic acid and D-lysine (D-GL). J Immunol. 1975 Feb;114(2 Pt 2):872–876. [PubMed] [Google Scholar]
  11. Golan D. T., Borel Y. Nonantigenicity and immunologic tolerance: the role of the carrier in the induction of tolerance to the hapten. J Exp Med. 1971 Oct 1;134(4):1046–1061. doi: 10.1084/jem.134.4.1046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goldman J. A., Litwin A., Adams L. E., Krueger R. C., Hess E. V. Cellular immunity to nuclear antigens in systemic lupus erythematosus. J Clin Invest. 1972 Oct;51(10):2669–2677. doi: 10.1172/JCI107085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Koffler D., Agnello V., Thoburn R., Kunkel H. G. Systemic lupus erythematosus: prototype of immune complex nephritis in man. J Exp Med. 1971 Sep 1;134(3 Pt 2):169s–179s. [PubMed] [Google Scholar]
  15. Koffler D., Carr R. I., Agnello V., Fiezi T., Kunkel H. G. Antibodies to polynucleotides: distribution in human serums. Science. 1969 Dec 26;166(3913):1648–1649. doi: 10.1126/science.166.3913.1648. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Morimoto C., Reinherz E. L., Nadler L. M., Distaso J. A., Steinberg A. D., Schlossman S. F. Comparison in T- and B-cell markers in patients with Sjögren's syndrome and systemic lupus erythematosus. Clin Immunol Immunopathol. 1982 Feb;22(2):270–278. doi: 10.1016/0090-1229(82)90043-5. [DOI] [PubMed] [Google Scholar]
  19. Morimoto C., Reinherz E. L., Schlossman S. F. Primary in vitro anti-KLH antibody formation by peripheral blood lymphocytes in man: detection with a radioimmunoassay. J Immunol. 1981 Aug;127(2):514–517. [PubMed] [Google Scholar]
  20. Morimoto C., Reinherz E. L., Schlossman S. F. Regulation of in vitro primary anti-DNP antibody production by functional subsets of T lymphocytes in man. J Immunol. 1981 Jul;127(1):69–73. [PubMed] [Google Scholar]
  21. 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]
  22. Papalian M., Lafer E., Wong R., Stollar B. D. Reaction of systemic lupus erythematosus antinative DNA antibodies with native DNA fragments from 20 to 1,200 base pairs. J Clin Invest. 1980 Feb;65(2):469–477. doi: 10.1172/JCI109690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Parker L. P., Hahn B. H., Osterland C. K. Modification of NZB-NZW F1 autoimmune disease by development of tolerance to DNA. J Immunol. 1974 Jul;113(1):292–297. [PubMed] [Google Scholar]
  24. Rosenthal C. J., Franklin E. C. Depression of cellular-mediated immunity in systemic lupus erythematosus. relation to disease activity. Arthritis Rheum. 1975 May-Jun;18(3):207–217. doi: 10.1002/art.1780180303. [DOI] [PubMed] [Google Scholar]
  25. Sagawa A., Abdou N. I. Suppressor-cell dysfunction in systemic lupus erythematosus. Cells involved and in vitro correction. J Clin Invest. 1978 Oct;62(4):789–796. doi: 10.1172/JCI109190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sakane T., Steinberg A. D., Green I. Studies of immune functions of patients with systemic lupus erythematosus. I. Dysfunction of suppressor T-cell activity related to impaired generation of, rather than response to, suppressor cells. Arthritis Rheum. 1978 Jul-Aug;21(6):657–664. doi: 10.1002/art.1780210608. [DOI] [PubMed] [Google Scholar]
  27. Steinberg A. D., Talal N. Suppression of antibodies to nucleic acids with polyinosinic-polycytidylic acid and cyclophosphamide in murine lupus. Clin Exp Immunol. 1970 Nov;7(5):687–691. [PMC free article] [PubMed] [Google Scholar]
  28. Talal N., Steinberg A. D., Daley G. G. Inhibition of antigodies binding polyinosinic-polycytidylic acid in human and mouse lupus sera by viral and synthetic ribonucleic acids. J Clin Invest. 1971 Jun;50(6):1248–1252. doi: 10.1172/JCI106602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tan E. M., Schur P. H., Carr R. I., Kunkel H. G. Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J Clin Invest. 1966 Nov;45(11):1732–1740. doi: 10.1172/JCI105479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vaughan J. H., Chihara T. Lymphocyte function in rheumatic disorders. Arch Intern Med. 1975 Oct;135(10):1324–1328. [PubMed] [Google Scholar]

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