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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1977 Jan;27(1):100–110.

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.

D A Horwitz, M A Garrett, A H Craig
PMCID: PMC1540902  PMID: 849643

Abstract

Methodological problems which affect the assessment of humoral effects on mitogenic reactivity include: (1) the source and concentration of serum used to support cell cultures; (2) the day to-day variability of inhibitory effects and (3) the specific activity of [3H]thymidine added to the culture. These problems were alleviated by addition of half concentration (7-5%) of pooled normal human serum to all cultures, the intoruction of anti-lymphocyte serum as a suitable internal control for monitoring the suppressability of lymphocytes and a reduction of specific activity of the [3H]thymidine to 1-3 C2/mM. Inhibitory factors were loosely bound to the lymphocyte surface and eluted off after incubation at 37 degrees C for 1 hr. Cells from twenty-five subjects and paired controls were cultured simultaneously in medium containing either 15% normal human serum (NHS) or 7-5% patient and 7-5% NHS. The cells were stimulated with various dilutions of phytohaemagglutinin, Con A or pokeweed mitogen. Lupus serums suppressed the reactivity of autologous lymphocytes to PHA and pokeweed mitogen. Serums from subjects with RA and scleroderma did not significantly inhibit blastogenesis of autologous lymphocytes. One-half of the lupus serums significantly inhibited the reactivity of homologous lymphocytes to two of three mitogens. Only one of eight scleroderma serums and none of twelve RA serums and none of twelve RA serums had this effect. All patients serums were examined for antilymphocyte antibodies by microcytotoxicity and immunofluorescent techniques. These antibodies were usually found in SLE, and were often observed in subjects with rheumatoid arthritis but not scleroderma. A firm relationship between serum suppressors of lymphocyte blastogenesis and anti-lymphocyte antibodies was not found.

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Selected References

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  1. Brochier J., Revillard J. P. In vitro stimulation or inhibition of lymphocyte activation by antilymphocyte serum. Transplant Proc. 1971 Mar;3(1):788–792. [PubMed] [Google Scholar]
  2. Brooks W. H., Netsky M. G., Normansell D. E., Horwitz D. A. Depressed cell-mediated immunity in patients with primary intracranial tumors. Characterization of a humoral immunosuppressive factor. J Exp Med. 1972 Dec 1;136(6):1631–1647. doi: 10.1084/jem.136.6.1631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burger D. R., Wilson B. J., Malley A., Vetto R. M. The effect of antilymphocyte antibody on lymphocyte transformation. Selective suppression of mitogen, mixed lymphocyte culture, and antigen stimulation of human lymphocytes. Transplantation. 1974 Jun;17(6):541–550. doi: 10.1097/00007890-197406000-00001. [DOI] [PubMed] [Google Scholar]
  4. Crout J. E., Hepburn B., Ritts R. E., Jr Suppression of lymphocyte transformation after aspirin ingestion. N Engl J Med. 1975 Jan 30;292(5):221–223. doi: 10.1056/NEJM197501302920501. [DOI] [PubMed] [Google Scholar]
  5. Gatti R. A., Yunis E. J., Good R. A. Characterization of a serum inhibitor of MLC reactions. Clin Exp Immunol. 1973 Mar;13(3):427–437. [PMC free article] [PubMed] [Google Scholar]
  6. Greaves M. F., Roitt I. M., Zamir R., Carnaghan R. B. Effect of anti-lymphocyte serum on responses of human peripheral-blood lymphocytes to specific and non-specific stimulants in vitro. Lancet. 1967 Dec 23;2(7530):1317–1319. doi: 10.1016/s0140-6736(67)90909-9. [DOI] [PubMed] [Google Scholar]
  7. Horwitz D. A., Cousar J. B. A relationship between impaired cellular immunity humoral suppression of lymphocyte function and severity of systemic lupus erythematosus. Am J Med. 1975 Jun;58(6):829–835. doi: 10.1016/0002-9343(75)90639-7. [DOI] [PubMed] [Google Scholar]
  8. Horwitz D. A., Garrett M. A. Lymphocyte reactivity to mitogens in subjects with systemic lupus erythematosus, rheumatoid arthritis and scleroderma. Clin Exp Immunol. 1977 Jan;27(1):92–99. [PMC free article] [PubMed] [Google Scholar]
  9. Horwitz D. A., Lobo P. I. Characterizaiton of two populations of human lymphocytes bearing easily detectable surface immunoglobulin. J Clin Invest. 1975 Dec;56(6):1464–1472. doi: 10.1172/JCI108227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huskisson E. C., Scott J., Balme H. W., Dieppe P. A., Trapnell J., Willoughby D. A. Immunostimulant therapy with levamisole for rheumatoid arthritis. Lancet. 1976 Feb 21;1(7956):393–395. doi: 10.1016/s0140-6736(76)90218-x. [DOI] [PubMed] [Google Scholar]
  11. Janossy G., Greaves M. F., Doenhoff M. J., Snajdr J. Lymphocyte activation. V. Quantitation of the proliferative responses to mitogens using defined T and B cell populations. Clin Exp Immunol. 1973 Aug;14(4):581–596. [PMC free article] [PubMed] [Google Scholar]
  12. Lance E. M., Knight S. C. Immunologic reactivity in rheumatoid arthritis. Response to mitogens. Arthritis Rheum. 1974 Sep-Oct;17(5):513–520. doi: 10.1002/art.1780170504. [DOI] [PubMed] [Google Scholar]
  13. Leventhal B. G., Waldorf D. S., Talal N. Impaired Lymphocyte Transformation and Delayed Hypersensitivity in Sjögren's Syndrome. J Clin Invest. 1967 Aug;46(8):1338–1345. doi: 10.1172/JCI105626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mangi R. J., Dwyer J. M., Kantor F. S. The effect of plasma upon lymphocyte response in vitro. Demonstration of a humoral inhibitor in patients with sarcoidosis. Clin Exp Immunol. 1974 Dec;18(4):519–528. [PMC free article] [PubMed] [Google Scholar]
  15. Opelz G., Terasaki P. I., Hirata A. A. Suppression of lymphocyte transformation by aspirin. Lancet. 1973 Sep 1;2(7827):478–480. doi: 10.1016/s0140-6736(73)92073-4. [DOI] [PubMed] [Google Scholar]
  16. Pachman L. M., Esterly N. B., Peterson R. D. The effect of salicylate on the metabolism of normal and stimulated human lymphocytes in vitro. J Clin Invest. 1971 Jan;50(1):226–230. doi: 10.1172/JCI106478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Suciu-Foca N., Buda J. A., Thiem T., Reemtsma K. Impaired responsiveness of lymphocytes in patients with systemic lupus erythematosus. Clin Exp Immunol. 1974 Nov;18(3):295–301. [PMC free article] [PubMed] [Google Scholar]
  18. Terasaki P. I., Mottironi V. D., Barnett E. V. Cytotoxins in disease. Autocytotoxins in lupus. N Engl J Med. 1970 Oct 1;283(14):724–728. doi: 10.1056/NEJM197010012831403. [DOI] [PubMed] [Google Scholar]
  19. Waxman J., Lockshin M. D., Schnapp J. J., Doneson I. N. Cellular immunity in rheumatic diseases. I. Rheumatoid arthritis. Arthritis Rheum. 1973 Jul-Aug;16(4):499–506. doi: 10.1002/art.1780160410. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Williams R. C., Jr, Lies R. B., Messner R. P. Inhibition of mixed leukocyte culture responses by serum and gamma-globulin fractions from certain patients with connective tissue disorders. Arthritis Rheum. 1973 Sep-Oct;16(5):597–605. doi: 10.1002/art.1780160504. [DOI] [PubMed] [Google Scholar]
  22. Winchester R. J., Winfield J. B., Siegal F., Wernet P., Bentwich Z., Kunkel H. G. Analyses of lymphocytes from patients with rheumatoid arthritis and systemic lupus erythematosus. Occurrence of interfering cold-reactive antilymphocyte antibodies. J Clin Invest. 1974 Nov;54(5):1082–1092. doi: 10.1172/JCI107852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Winfield J. B., Winchester R. J., Wernet P., Fu S. M., Kunkel H. G. Nature of cold-reactive antibodies to lymphocyte surface determinants in systemic lupus erythematosus. Arthritis Rheum. 1975 Jan-Feb;18(1):1–8. doi: 10.1002/art.1780180101. [DOI] [PubMed] [Google Scholar]

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