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. 1987 Nov;70(2):336–344.

Multiple sclerosis: II. Effects of prothymosin alpha on the autologous and allogeneic MLR in patients with multiple sclerosis.

G J Reclos 1, C N Baxevanis 1, C Sfagos 1, C Papageorgiou 1, G C Tsokos 1, M Papamichail 1
PMCID: PMC1542094  PMID: 2962790

Abstract

We have recently demonstrated that peripheral blood monocytes from patients with multiple sclerosis (MS) have a defect in stimulating autologous and allogeneic T lymphocytes. This defect was found to correlate with disease activity. In this report we demonstrate that prothymosin alpha (ProT alpha), a rat thymus fraction 5 polypeptide, restores the MS monocyte stimulatory defect. The concentrations of ProT alpha which induced optimal enhancement of the mixed lymphocyte responses (MLR) were significantly higher when monocytes from patients with active disease were used as stimulators than when monocytes from patients with inactive disease were used. T4+ cells tested with autologous stimulatory monocytes harvested from an inactive stage of MS exhibited considerably higher proliferative responses than when stimulated with autologous monocytes obtained from an acute relapse. The decreased autologous proliferation of T4+ cells in MS patients was restored to normal levels after preincubation with ProT alpha in the environment of autologous monocytes. Our results demonstrate that ProT alpha is capable of fully restoring the deficient stimulatory function of MS monocytes and monocyte-associated functional defects of MS-derived T4+ cells.

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Selected References

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

  1. Arnason B. G., Antel J. Suppressor cell function in multiple sclerosis. Ann Immunol (Paris) 1978 Feb-Mar;129(2-3):159–170. [PubMed] [Google Scholar]
  2. Baxevanis C. N., Ioannides C. D., Papamichail M. The role of self-Ia antigens in the murine mixed lymphocyte response. Eur J Immunol. 1986 Apr;16(4):361–365. doi: 10.1002/eji.1830160408. [DOI] [PubMed] [Google Scholar]
  3. Baxevanis C. N., Perez S., Kokkinopoulos D., Papamichail M. The biological effect of three thymosin fraction 5 polypeptides in the murine mixed lymphocyte reaction. Immunology. 1985 Apr;54(4):723–730. [PMC free article] [PubMed] [Google Scholar]
  4. Baxevanis C. N., Reclos G. J., Perez S., Kokkinopoulos D., Papamichail M. Immunoregulatory effects of fraction 5 thymus peptides. I. Thymosin alpha 1 enhances while thymosin beta 4 suppresses the human autologous and allogeneic mixed lymphocyte reaction. Immunopharmacology. 1987 Apr;13(2):133–141. doi: 10.1016/0162-3109(87)90050-6. [DOI] [PubMed] [Google Scholar]
  5. Baxevanis C. N., Reclos G. J., Sfagos C., Doufexis E., Papageorgiou C., Papamichail M. Multiple sclerosis: I. Monocyte stimulatory defect in mixed lymphocyte reaction associated with clinical disease activity. Clin Exp Immunol. 1987 Feb;67(2):362–371. [PMC free article] [PubMed] [Google Scholar]
  6. Caldarella J., Goodall G. J., Felix A. M., Heimer E. P., Salvin S. B., Horecker B. L. Thymosin alpha 11: a peptide related to thymosin alpha 1 isolated from calf thymosin fraction 5. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7424–7427. doi: 10.1073/pnas.80.24.7424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Farrar W. L., Cleveland J. L., Beckner S. K., Bonvini E., Evans S. W. Biochemical and molecular events associated with interleukin 2 regulation of lymphocyte proliferation. Immunol Rev. 1986 Aug;92:49–65. doi: 10.1111/j.1600-065x.1986.tb01493.x. [DOI] [PubMed] [Google Scholar]
  9. Goldstein A. L., Low T. L., McAdoo M., McClure J., Thurman G. B., Rossio J., Lai C. Y., Chang D., Wang S. S., Harvey C. Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide. Proc Natl Acad Sci U S A. 1977 Feb;74(2):725–729. doi: 10.1073/pnas.74.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Greene W. C., Depper J. M., Krönke M., Leonard W. J. The human interleukin-2 receptor: analysis of structure and function. Immunol Rev. 1986 Aug;92:29–48. doi: 10.1111/j.1600-065x.1986.tb01492.x. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Haritos A. A., Goodall G. J., Horecker B. L. Prothymosin alpha: isolation and properties of the major immunoreactive form of thymosin alpha 1 in rat thymus. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1008–1011. doi: 10.1073/pnas.81.4.1008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Haritos A. A., Salvin S. B., Blacher R., Stein S., Horecker B. L. Parathymosin alpha: a peptide from rat tissues with structural homology to prothymosin alpha. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1050–1053. doi: 10.1073/pnas.82.4.1050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. 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]
  17. Low T. L., Goldstein A. L. The chemistry and biology of thymosin. II. Amino acid sequence analysis of thymosin alpha1 and polypeptide beta1. J Biol Chem. 1979 Feb 10;254(3):987–995. [PubMed] [Google Scholar]
  18. Low T. L., Hu S. K., Goldstein A. L. Complete amino acid sequence of bovine thymosin beta 4: a thymic hormone that induces terminal deoxynucleotidyl transferase activity in thymocyte populations. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1162–1166. doi: 10.1073/pnas.78.2.1162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Noorloos A. A., van Beek A. A., Melief C. J. Cryopreservation of cells for immunological typing of non-Hodgkin's lymphomas. Cancer Res. 1980 Aug;40(8 Pt 1):2890–2894. [PubMed] [Google Scholar]
  20. Papiernik M., Dombret H., Stefanos S., Wietzerbin J. Control of Ia antigen expression on phagocytic cells of the thymic reticulum by interferon-gamma and prostaglandins. Eur J Immunol. 1986 Mar;16(3):296–300. doi: 10.1002/eji.1830160316. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Sztein M. B., Steeg P. S., Johnson H. M., Oppenheim J. J. Regulation of human peripheral blood monocyte DR antigen expression in vitro by lymphokines and recombinant interferons. J Clin Invest. 1984 Feb;73(2):556–565. doi: 10.1172/JCI111243. [DOI] [PMC free article] [PubMed] [Google Scholar]

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