Abstract
Polymyositis/dermatomyositis (PM/DM) is an autoimmune disorder of unknown aetiology. In order to study whether immunoregulatory abnormalities might be involved in this autoimmune state, we investigated the autologous mixed lymphocyte reaction (AMLR) and concanavalin A-induced suppressor cell function (Con A-induced suppression) in adult patients with primary PM/DM. We found the AMLR to be significantly depressed in patients; responsiveness could not be enhanced by increasing the numbers of non-T stimulator cells in culture, nor by varying the day on which cultures were harvested. Con A-induced suppression of T cell proliferative responses to mitogenic stimuli was normal. These findings implicate abnormal immunoregulation in the pathophysiology of PM/DM. Further, the dissociation of AMLR reactivity from Con A-inducible suppression suggests that events important for immunoregulatory competence may occur in the AMLR culture, despite the absence of an observed proliferative response.
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- Battisto J. R., Ponzio N. M. Autologous and syngeneic mixed lymphocyte reactions and their immunological significance. Prog Allergy. 1981;28:160–192. [PubMed] [Google Scholar]
- Bohan A., Peter J. B., Bowman R. L., Pearson C. M. Computer-assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine (Baltimore) 1977 Jul;56(4):255–286. doi: 10.1097/00005792-197707000-00001. [DOI] [PubMed] [Google Scholar]
- Carpenter S., Karpati G., Heller I., Eisen A. Inclusion body myositis: a distinct variety of idiopathic inflammatory myopathy. Neurology. 1978 Jan;28(1):8–17. doi: 10.1212/wnl.28.1.8. [DOI] [PubMed] [Google Scholar]
- Dawkins R. L. Experimental autoallergic myositis, polymyositis and myasthenia gravis. Autoimmune muscle disease associated with immunodeficiency and neoplasia. Clin Exp Immunol. 1975 Aug;21(2):185–201. [PMC free article] [PubMed] [Google Scholar]
- Dawkins R. L., Mastaglia F. L. Cell-mediated cytotoxicity to muscle in polymyositis. Effect of immunosuppression. N Engl J Med. 1973 Mar 1;288(9):434–438. doi: 10.1056/NEJM197303012880903. [DOI] [PubMed] [Google Scholar]
- Esiri M. M., MacLennan I. C., Hazleman B. L. Lymphocyte sensitivity to skeletal muscle in patients with polymyositis and other disorders. Clin Exp Immunol. 1973 May;14(1):25–35. [PMC free article] [PubMed] [Google Scholar]
- Fineman S. M., Mudawwar F. B., Geha R. S. Characteristics and mechanisms of action of the concanavalin A-activated suppressor cell in man. Cell Immunol. 1979 Jun;45(1):120–132. doi: 10.1016/0008-8749(79)90367-8. [DOI] [PubMed] [Google Scholar]
- Glimcher L. H., Shevach E. M. Production of autoreactive I region-restricted T cell hybridomas. J Exp Med. 1982 Aug 1;156(2):640–645. doi: 10.1084/jem.156.2.640. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haas D. C., Arnason B. G. Cell-mediated immunity in polymyositis. Creatine phosphokinase release from muscle cultures. Arch Neurol. 1974 Sep;31(3):192–196. doi: 10.1001/archneur.1974.00490390074008. [DOI] [PubMed] [Google Scholar]
- Hahn B. H., MacDermott R. P., Jacobs S. B., Pletscher L. S., Beale M. G. Immunosuppressive effects of low doses of glucocorticoids: effects on autologous and allogeneic mixed leukocyte reactions. J Immunol. 1980 Jun;124(6):2812–2817. [PubMed] [Google Scholar]
- Hellmann D., Stobo J. The autologous mixed lymphocyte reaction. A precautionary note. Arthritis Rheum. 1982 Feb;25(2):121–125. doi: 10.1002/art.1780250201. [DOI] [PubMed] [Google Scholar]
- Huber C., Merkenschlager M., Gattringer C., Royston I., Fink U., Braunsteiner H. Human autologous mixed lymphocyte reactivity is primarily specific for xenoprotein determinants adsorbed to antigen-presenting cells during rosette formation with sheep erythrocytes. J Exp Med. 1982 Apr 1;155(4):1222–1227. doi: 10.1084/jem.155.4.1222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Innes J. B., Kuntz M. M., Kim Y. T., Weksler M. E. Induction of suppressor activity in the autologous mixed lymphocyte reaction and in cultures with concanavalin A. J Clin Invest. 1979 Dec;64(6):1608–1613. doi: 10.1172/JCI109622. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson R. L., Fink C. W., Ziff M. Lymphotoxin formation by lymphocytes and muscle in polymyositis. J Clin Invest. 1972 Sep;51(9):2435–2449. doi: 10.1172/JCI107057. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kakulas B. A. Destruction of differentiated muscle cultures by sensitised lymphoid cells. J Pathol Bacteriol. 1966 Apr;91(2):495–503. doi: 10.1002/path.1700910225. [DOI] [PubMed] [Google Scholar]
- Kuntz M. M., Innes J. B., Weksler M. E. Lymphocyte transformation induced by autologous cells. IV. Human T-lymphocyte proliferation induced by autologous or allogeneic non-T lymphocytes. J Exp Med. 1976 May 1;143(5):1042–1054. doi: 10.1084/jem.143.5.1042. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacDermott R. P., Stacey M. C. Further characterization of the human autologous mixed leukocyte reaction (MLR). J Immunol. 1981 Feb;126(2):729–734. [PubMed] [Google Scholar]
- Miyasaka N., Sauvezie B., Pierce D. A., Daniels T. E., Talal N. Decreased autologous mixed lymphocyte reaction in Sjögren's syndrome. J Clin Invest. 1980 Nov;66(5):928–933. doi: 10.1172/JCI109960. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moody C. E., Casazza B. A., Christenson W. N., Weksler M. E. Lymphocyte transformation induced by autologous cells. VIII. Impaired autologous mixed lymphocyte reactivity in patients with acute infectious mononucleosis. J Exp Med. 1979 Dec 1;150(6):1448–1455. doi: 10.1084/jem.150.6.1448. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Partridge T. A., Smith P. D. A quantitative test to detect lymphocytes sensitized against the surface of muscle cells. Clin Exp Immunol. 1976 Jul;25(1):139–143. [PMC free article] [PubMed] [Google Scholar]
- Sakane T., Green I. Human suppressor T cells induced by concanavalin A: suppressor T cells belong to distinctive T cell subclasses. J Immunol. 1977 Sep;119(3):1169–1178. [PubMed] [Google Scholar]
- Sakane T., Green I. Specificity and suppressor function of human T cells responsive to autologous non-T cells. J Immunol. 1979 Aug;123(2):584–589. [PubMed] [Google Scholar]
- 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]
- 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]
- Shevach E. M. The function of macrophages in antigen recognition by guinea pig T lymphocytes. III. Genetic analysis of the antigens mediating macrophage-T lymphocyte interaction. J Immunol. 1976 May;116(5):1482–1489. [PubMed] [Google Scholar]
- 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]
- Smith C. I., Svejgaard A. Concanavalin-A-induced suppressor lymphocytes in normal individuals. Scand J Immunol. 1981;13(5):483–492. doi: 10.1111/j.1365-3083.1981.tb00160.x. [DOI] [PubMed] [Google Scholar]
- Smith J. B., Talal N. Significance of self-recognition and interleukin-2 for immunoregulation, autoimmunity and cancer. Scand J Immunol. 1982 Oct;16(4):269–278. doi: 10.1111/j.1365-3083.1982.tb00723.x. [DOI] [PubMed] [Google Scholar]
- Smolen J. S., Chused T. M., Novotny E. A., Steinberg A. D. The human autologous mixed lymphocyte reaction. III. Immune circuits. J Immunol. 1982 Sep;129(3):1050–1053. [PubMed] [Google Scholar]
- Weksler M. E., Kozak R. Lymphocyte transformation induced by autologous cells. V. Generation of immunologic memory and specificity during the autologous mixed lymphocyte reaction. J Exp Med. 1977 Dec 1;146(6):1833–1838. doi: 10.1084/jem.146.6.1833. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weksler M. E., Moody C. E., Jr, Kozak R. W. The autologous mixed-lymphocyte reaction. Adv Immunol. 1981;31:271–312. doi: 10.1016/s0065-2776(08)60923-2. [DOI] [PubMed] [Google Scholar]
- Ziff M., Johnson R. L. Polymyositis and cell-mediated immunity. N Engl J Med. 1973 Mar 1;288(9):465–466. doi: 10.1056/NEJM197303012880910. [DOI] [PubMed] [Google Scholar]