Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1987 Feb;67(2):362–371.

Multiple sclerosis: I. Monocyte stimulatory defect in mixed lymphocyte reaction associated with clinical disease activity.

C N Baxevanis, G J Reclos, C Sfagos, E Doufexis, C Papageorgiou, M Papamichail
PMCID: PMC1542579  PMID: 2955971

Abstract

To investigate whether abnormalities of cellular immune responses are associated with multiple sclerosis (MS), we tested peripheral blood mononuclear cells (PBMC) or T cells, and monocytes from MS patients as responder and stimulatory cells respectively, in the allogeneic (allo-MLR) and autologous mixed lymphocyte reaction (auto-MLR). We found that PBMC or T cells from all MS patients were able to develop strong proliferation against allogeneic monocytes derived from normal individuals. Moreover, the capacity of monocytes from MS patients to act as accessory cells for autologous T cells in the allo-MLR was indistinguishable from that of normal donors. In contrast, monocytes from patients with active MS were not able to stimulate responder cell proliferation either in allo-MLR or in auto-MLR. This monocyte defect was partially restored in the inactive stage of the disease. In conclusion our results show that the stimulatory capacity of monocytes from MS patients in the MLR is closely associated with the clinical stage of MS. The observed monocyte defect may be helpful in understanding the pathogenesis of MS and can be used in evaluating the outcome of the disease activity.

Full text

PDF
362

Selected References

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

  1. Abramsky O., Lisak R. P., Silberberg D. H., Pleasure D. E. Antibodies to oligodendroglia in patients with multiple sclerosis. N Engl J Med. 1977 Dec 1;297(22):1207–1211. doi: 10.1056/NEJM197712012972204. [DOI] [PubMed] [Google Scholar]
  2. Antel J. P., Arnason B. G., Medof M. E. Suppressor cell function in multiple sclerosis: correlation with clinical disease activity. Ann Neurol. 1979 Apr;5(4):338–342. doi: 10.1002/ana.410050406. [DOI] [PubMed] [Google Scholar]
  3. Ballieux R. E., Heijnen C. J. Immunoregulatory T cell subpopulations in man: dissection by monoclonal antibodies and Fc-receptors. Immunol Rev. 1983;74:5–28. doi: 10.1111/j.1600-065x.1983.tb01082.x. [DOI] [PubMed] [Google Scholar]
  4. Baxevanis C. N., Ishii N., Nagy Z. A., Klein J. H-2-controlled suppression of T cell response to lactate dehydrogenase B. Characterization of the lactate dehydrogenase B suppressor pathway. J Exp Med. 1982 Sep 1;156(3):822–833. doi: 10.1084/jem.156.3.822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Breard J., Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody reactive with human peripheral blood monocytes. J Immunol. 1980 Apr;124(4):1943–1948. [PubMed] [Google Scholar]
  6. Coyle P. K., Brooks B. R., Hirsch R. L., Cohen S. R., O'Donnell P., Johnson R. T., Wolinsky J. S. Cerebrospinal-fluid lymphocyte populations and immune complexes in active multiple sclerosis. Lancet. 1980 Aug 2;2(8188):229–232. doi: 10.1016/s0140-6736(80)90121-x. [DOI] [PubMed] [Google Scholar]
  7. Dock N. L., Davey F. R. Peripheral blood monocytes in the autologous mixed lymphocyte reaction. Clin Immunol Immunopathol. 1980 Sep;17(1):123–131. doi: 10.1016/0090-1229(80)90080-x. [DOI] [PubMed] [Google Scholar]
  8. Hafler D. A., Buchsbaum M., Weiner H. L. Decreased autologous mixed lymphocyte reaction in multiple sclerosis. J Neuroimmunol. 1985 Oct;9(6):339–347. doi: 10.1016/s0165-5728(85)80034-5. [DOI] [PubMed] [Google Scholar]
  9. Hirsch R. L. Defective autologous mixed lymphocyte reactivity in multiple sclerosis. Clin Exp Immunol. 1986 Apr;64(1):107–113. [PMC free article] [PubMed] [Google Scholar]
  10. Hirsch R. L., Ordonez J., Panitch H. S., Johnson K. P. T8 antigen density on peripheral blood lymphocytes remains unchanged during exacerbations of multiple sclerosis. J Neuroimmunol. 1985 Oct;9(6):391–398. doi: 10.1016/s0165-5728(85)80038-2. [DOI] [PubMed] [Google Scholar]
  11. Huddlestone J. R., Oldstone M. B. Suppressor T cells are activated in vivo in patients with multiple sclerosis coinciding with remission from acute attack. J Immunol. 1982 Sep;129(3):915–917. [PubMed] [Google Scholar]
  12. Johnson K. P., Nelson B. J. Multiple sclerosis: diagnostic usefulness of cerebrospinal fluid. Ann Neurol. 1977 Nov;2(5):425–431. doi: 10.1002/ana.410020515. [DOI] [PubMed] [Google Scholar]
  13. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  14. Kastrukoff L. F., Paty D. W. A serial study of peripheral blood T lymphocyte subsets in relapsing-remitting multiple sclerosis. Ann Neurol. 1984 Mar;15(3):250–256. doi: 10.1002/ana.410150308. [DOI] [PubMed] [Google Scholar]
  15. Kastrukoff L. F., Paty D. W. A two-label microfluorometric analysis of the expression of OKT5 and Leu 2a antigens on peripheral blood lymphocytes in patients with multiple sclerosis. J Neuroimmunol. 1984 Apr;6(2):85–92. doi: 10.1016/0165-5728(84)90029-8. [DOI] [PubMed] [Google Scholar]
  16. Knight S. C. Cellular immunity in multiple sclerosis. Br Med Bull. 1977 Jan;33(1):45–50. doi: 10.1093/oxfordjournals.bmb.a071395. [DOI] [PubMed] [Google Scholar]
  17. Koide Y., Awashima F., Yoshida T. O., Takenouchi T., Wakisaka A., Moriuchi J., Aizawa M. The role of three distinct Ia-like antigen molecules in human T cell proliferative responses: effect of monoclonal anti-Ia-like antibodies. J Immunol. 1982 Sep;129(3):1061–1069. [PubMed] [Google Scholar]
  18. Kumagai K., Itoh K., Hinuma S., Tada M. Pretreatment of plastic Petri dishes with fetal calf serum. A simple method for macrophage isolation. J Immunol Methods. 1979;29(1):17–25. doi: 10.1016/0022-1759(79)90121-2. [DOI] [PubMed] [Google Scholar]
  19. Kung P., Goldstein G., Reinherz E. L., Schlossman S. F. Monoclonal antibodies defining distinctive human T cell surface antigens. Science. 1979 Oct 19;206(4416):347–349. doi: 10.1126/science.314668. [DOI] [PubMed] [Google Scholar]
  20. Morimoto C., Reinherz E. L., Todd R. F., Distaso J. A., Schlossman S. F. Generation of antigen-specific suppressor cells in vitro in man. J Immunol. 1983 Sep;131(3):1209–1213. [PubMed] [Google Scholar]
  21. Naides S. J., Redelman D., Zvaifler N. J. The role of xenoantigen in the human autologous mixed lymphocyte reaction: ability to respond in the absence of exposure to xenoantigen depends on the method of T-cell preparation. Clin Immunol Immunopathol. 1985 Feb;34(2):216–226. doi: 10.1016/0090-1229(85)90026-1. [DOI] [PubMed] [Google Scholar]
  22. Opelz G., Terasaki P., Myers L., Ellison G., Ebers G., Zabriskie J., Weiner H., Kempe H., Sibley W. The association of HLA antigens A3, B7, and DW2 with 330 multiple sclerosis patients in the United States. Tissue Antigens. 1977 Jan;9(1):54–58. doi: 10.1111/j.1399-0039.1977.tb01080.x. [DOI] [PubMed] [Google Scholar]
  23. Panitch H. S., Francis G. S. T-lymphocyte subsets in cerebrospinal fluid in multiple sclerosis. N Engl J Med. 1982 Aug 26;307(9):560–561. doi: 10.1056/nejm198208263070921. [DOI] [PubMed] [Google Scholar]
  24. Paty D. W., Kastrukoff L. F. Suppressor T cells in MS: do changes in numbers vary with clinical activity? Ann N Y Acad Sci. 1984;436:266–270. doi: 10.1111/j.1749-6632.1984.tb14798.x. [DOI] [PubMed] [Google Scholar]
  25. Paty D. W., Kastrukoff L., Morgan N., Hiob L. Suppressor T-lymphocytes in multiple sclerosis: analysis of patients with acute relapsing and chronic progressive disease. Ann Neurol. 1983 Oct;14(4):445–449. doi: 10.1002/ana.410140408. [DOI] [PubMed] [Google Scholar]
  26. Reinherz E. L., Weiner H. L., Hauser S. L., Cohen J. A., Distaso J. A., Schlossman S. F. Loss of suppressor T cells in active multiple sclerosis. Analysis with monoclonal antibodies. N Engl J Med. 1980 Jul 17;303(3):125–129. doi: 10.1056/NEJM198007173030303. [DOI] [PubMed] [Google Scholar]
  27. Rice G. P., Finney D., Braheny S. L., Knobler R. L., Sipe J. C., Oldstone M. B. Disease activity markers in multiple sclerosis. Another look at suppressor cells defined by monoclonal antibodies OKT4, OKT5, and OKT8. J Neuroimmunol. 1984 Apr;6(2):75–84. doi: 10.1016/0165-5728(84)90028-6. [DOI] [PubMed] [Google Scholar]
  28. Romain P. L., Morimoto C., Daley J. F., Palley L. S., Reinherz E. L., Schlossman S. F. Reactivity of inducer cell subsets and T8-cell activation during the human autologous mixed lymphocyte reaction. Clin Immunol Immunopathol. 1984 Jan;30(1):117–128. doi: 10.1016/0090-1229(84)90012-6. [DOI] [PubMed] [Google Scholar]
  29. Schocket A. L., Weiner H. L., Walker J., McIntosh K., Kohler P. F. Lymphocytotoxic antibodies in multiple sclerosis. Clin Immunol Immunopathol. 1977 Jan;7(1):15–23. doi: 10.1016/0090-1229(77)90025-3. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Smolen J. S., Luger T. A., Chused T. M., Steinberg A. D. Responder cells in the human autologous mixed lymphocyte reaction. J Clin Invest. 1981 Dec;68(6):1601–1604. doi: 10.1172/JCI110416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Smolen J. S., Siminovitch K., Luger T. A., Steinberg A. D. Responder cells in the human autologous mixed lymphocyte reaction (AMLR). Characterization and interactions in healthy individuals and patients with systemic lupus erythematosus. Behring Inst Mitt. 1983 May;(72):135–142. [PubMed] [Google Scholar]
  33. Thomas Y., Rogozinski L., Chess L. Relationship between human T cell functional heterogeneity and human T cell surface molecules. Immunol Rev. 1983;74:113–128. doi: 10.1111/j.1600-065x.1983.tb01086.x. [DOI] [PubMed] [Google Scholar]
  34. Weiner H. L., Hafler D. A., Fallis R. J., Johnson D., Ault K. A., Hauser S. L. Altered blood T-cell subsets in patients with multiple sclerosis. J Neuroimmunol. 1984 Apr;6(2):115–121. doi: 10.1016/0165-5728(84)90032-8. [DOI] [PubMed] [Google Scholar]
  35. Yam L. T., Li C. Y., Crosby W. H. Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol. 1971 Mar;55(3):283–290. doi: 10.1093/ajcp/55.3.283. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES