Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Aug;90(2):399–404. doi: 10.1172/JCI115874

Experimental allergic encephalomyelitis in cynomolgus monkeys. Quantitation of T cell responses in peripheral blood.

L Massacesi 1, N Joshi 1, D Lee-Parritz 1, A Rombos 1, N L Letvin 1, S L Hauser 1
PMCID: PMC443114  PMID: 1379611

Abstract

Chronic relapsing-remitting experimental allergic encephalomyelitis (EAE) was induced in cynomolgus monkeys by a single immunization with a homogenate of human brain white matter (BH) in adjuvant. Proliferative T lymphocyte responses to BH, to myelin basic protein (MBP), but not to proteolipid protein, were detected in peripheral blood mononuclear cells (PBMC) of all animals and persisted until their death or, in surviving animals, for greater than 10 mo postimmunization. Responses of higher magnitude tended to be associated with fatal, compared with nonfatal, episodes of clinical EAE. The frequency of MBP-reactive T cells in PBMC of animals with acute EAE was quantitated with a soft agar colony system; the ratio of T cells that proliferated specifically to MBP was estimated at between 5 and 20 per 10(6) PBMC. A similar frequency of peptide-specific T cells was estimated from PBMC of monkeys immunized with a synthetic 14-mer peptide corresponding to a region near the carboxy terminus of MBP. Thus, autoantigen-reactive T cells can be detected in the circulation throughout the course of chronic EAE, are predictive of disease severity, and occur at a frequency similar to that estimated to be present in humans with multiple sclerosis.

Full text

PDF
399

Selected References

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

  1. Allegretta M., Nicklas J. A., Sriram S., Albertini R. J. T cells responsive to myelin basic protein in patients with multiple sclerosis. Science. 1990 Feb 9;247(4943):718–721. doi: 10.1126/science.1689076. [DOI] [PubMed] [Google Scholar]
  2. Alvord E. C., Jr, Shaw C. M., Hruby S. Myelin basic protein treatment of experimental allergic encephalomyelitis in monkeys. Ann Neurol. 1979 Dec;6(6):469–473. doi: 10.1002/ana.410060603. [DOI] [PubMed] [Google Scholar]
  3. Behan P. O., Kies M. W., Lisak R. P., Sheremata W., Lamarche J. B. Immunologic mechanisms in experimental encephalomyelitis in nonhuman primates. Arch Neurol. 1973 Jul;29(1):4–9. doi: 10.1001/archneur.1973.00490250022002. [DOI] [PubMed] [Google Scholar]
  4. Deibler G. E., Martenson R. E., Kies M. W. Large scale preparation of myelin basic protein from central nervous tissue of several mammalian species. Prep Biochem. 1972;2(2):139–165. doi: 10.1080/00327487208061467. [DOI] [PubMed] [Google Scholar]
  5. Eylar E. H., Brostoff S., Jackson J., Carter H. Allergic encephalomyelitis in monkeys induced by a peptide from the A1 protein. Proc Natl Acad Sci U S A. 1972 Mar;69(3):617–619. doi: 10.1073/pnas.69.3.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fallis R. J., Powers M. L., Weiner H. L. Serial analysis of peripheral blood T-cell phenotypes and myelin basic protein reactivity in experimental allergic encephalomyelitis. Neurology. 1987 Apr;37(4):719–723. doi: 10.1212/wnl.37.4.719. [DOI] [PubMed] [Google Scholar]
  7. Fowler I. In vitro responses of peripheral blood lymphocytes in experimental allergic encephalomyelitis. J Immunol. 1972 Apr;108(4):903–906. [PubMed] [Google Scholar]
  8. Goldmuntz E. A., Brosnan C. F., Norton W. T. Prazosin treatment suppresses increased vascular permeability in both acute and passively transferred experimental autoimmune encephalomyelitis in the Lewis rat. J Immunol. 1986 Dec 1;137(11):3444–3450. [PubMed] [Google Scholar]
  9. Holtzman E., Freeman A. R., Kashner L. A. Stimulation-dependent alterations in peroxidase uptake at lobster neuromuscular junctions. Science. 1971 Aug 20;173(3998):733–736. doi: 10.1126/science.173.3998.733. [DOI] [PubMed] [Google Scholar]
  10. Johnson D., Hafler D. A., Fallis R. J., Lees M. B., Brady R. O., Quarles R. H., Weiner H. L. Cell-mediated immunity to myelin-associated glycoprotein, proteolipid protein, and myelin basic protein in multiple sclerosis. J Neuroimmunol. 1986 Nov;13(1):99–108. doi: 10.1016/0165-5728(86)90053-6. [DOI] [PubMed] [Google Scholar]
  11. Karkhanis Y. D., Carlo D. J., Brostoff S. W., Eylar E. H. Allergic encephalomyelitis. Isolation of an encephalitogenic peptide active in the monkey. J Biol Chem. 1975 Mar 10;250(5):1718–1722. [PubMed] [Google Scholar]
  12. Kibler R. F., Re P. K., McKneally S., Shapira R. Biological activity of an encephalitogenic fragment in the monkey. J Biol Chem. 1972 Feb 10;247(3):969–972. [PubMed] [Google Scholar]
  13. Lisak R. P., Zweiman B. In vitro and in vivo immune responses to homologous myelin basic protein in experimental allergic encephalomyelitis. Cell Immunol. 1974 Mar 30;11(1-3):212–220. doi: 10.1016/0008-8749(74)90021-5. [DOI] [PubMed] [Google Scholar]
  14. Lyman W. D., Kadish A. S., Raine C. S. Experimental allergic encephalomyelitis in the guinea pig: variation in peripheral blood lymphocyte responsiveness to myelin basic protein during disease development. Cell Immunol. 1981 Sep 15;63(2):409–416. doi: 10.1016/0008-8749(81)90019-8. [DOI] [PubMed] [Google Scholar]
  15. Martin R., Jaraquemada D., Flerlage M., Richert J., Whitaker J., Long E. O., McFarlin D. E., McFarland H. F. Fine specificity and HLA restriction of myelin basic protein-specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals. J Immunol. 1990 Jul 15;145(2):540–548. [PubMed] [Google Scholar]
  16. McFarlin D. E., Blank S. E., Kibler R. F. Recurrent experimental allergic encephalomyelitis in the Lewis rat. J Immunol. 1974 Aug;113(2):712–715. [PubMed] [Google Scholar]
  17. Olsson T., Zhi W. W., Höjeberg B., Kostulas V., Jiang Y. P., Anderson G., Ekre H. P., Link H. Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma. J Clin Invest. 1990 Sep;86(3):981–985. doi: 10.1172/JCI114800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ota K., Matsui M., Milford E. L., Mackin G. A., Weiner H. L., Hafler D. A. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature. 1990 Jul 12;346(6280):183–187. doi: 10.1038/346183a0. [DOI] [PubMed] [Google Scholar]
  19. Paterson P. Y. Molecular and cellular determinants of neuroimmunologic inflammatory disease. Fed Proc. 1982 Jul;41(9):2569–2576. [PubMed] [Google Scholar]
  20. Pettinelli C. B., McFarlin D. E. Adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice after in vitro activation of lymph node cells by myelin basic protein: requirement for Lyt 1+ 2- T lymphocytes. J Immunol. 1981 Oct;127(4):1420–1423. [PubMed] [Google Scholar]
  21. Ravkina L., Rogova V., Lazarenko L. Chronic experimental allergic encephalomyelitis in rhesus monkeys and its modification by treatment. J Neurol Sci. 1978 Oct;38(3):281–293. doi: 10.1016/0022-510x(78)90136-3. [DOI] [PubMed] [Google Scholar]
  22. Selmaj K., Nowak Z., Tchórzewski H. Multiple sclerosis: effect of myelin basic protein on interleukin 1, interleukin 2 production and interleukin 2 receptor expression in vitro. Clin Exp Immunol. 1988 Jun;72(3):428–433. [PMC free article] [PubMed] [Google Scholar]
  23. Shaw C. M., Alvord E. C., Jr, Hruby S. Chronic remitting-relapsing experimental allergic encephalomyelitis induced in monkeys with homologous myelin basic protein. Ann Neurol. 1988 Dec;24(6):738–748. doi: 10.1002/ana.410240608. [DOI] [PubMed] [Google Scholar]
  24. Sredni B., Tse H. Y., Schwartz R. H. Direct cloning and extended culture of antigen-specific MHC-restricted, proliferating T lymphocytes. Nature. 1980 Feb 7;283(5747):581–583. doi: 10.1038/283581a0. [DOI] [PubMed] [Google Scholar]
  25. Stohl W., Gonatas N. K. Chronic permeability of the central nervous system to mononuclear cells in experimental allergic encephalomyelitis in the Lewis rat. J Immunol. 1978 Sep;121(3):844–850. [PubMed] [Google Scholar]
  26. Traugott U., Raine C. S. Experimental allergic encephalomyelitis in inbred guinea pigs: correlation of decrease in early T cells with clinical signs in suppressed and unsuppressed animals. Cell Immunol. 1977 Nov;34(1):146–155. doi: 10.1016/0008-8749(77)90237-4. [DOI] [PubMed] [Google Scholar]
  27. Traugott U., Stone S. H., Raine C. S. Chronic relapsing experimental allergic encephalomyelitis. Correlation of circulating lymphocyte fluctuations with disease activity in suppressed and unsuppressed animals. J Neurol Sci. 1979 Mar;41(1):17–29. doi: 10.1016/0022-510x(79)90136-9. [DOI] [PubMed] [Google Scholar]
  28. Tuohy V. K., Lu Z., Sobel R. A., Laursen R. A., Lees M. B. Identification of an encephalitogenic determinant of myelin proteolipid protein for SJL mice. J Immunol. 1989 Mar 1;142(5):1523–1527. [PubMed] [Google Scholar]
  29. Vandenbark A. A., Gill T., Offner H. A myelin basic protein-specific T lymphocyte line that mediates experimental autoimmune encephalomyelitis. J Immunol. 1985 Jul;135(1):223–228. [PubMed] [Google Scholar]
  30. Watkins D. I., Kannagi M., Stone M. E., Letvin N. L. Major histocompatibility complex class I molecules of nonhuman primates. Eur J Immunol. 1988 Sep;18(9):1425–1432. doi: 10.1002/eji.1830180919. [DOI] [PubMed] [Google Scholar]
  31. Watkins D. I., Shadduck J. A., Hodi F. S., Stone M. E., Letvin N. L. Use of cDNA probes specific for the human MHC class II beta loci for tissue-typing nonhuman primates at their class II beta loci. Transplantation. 1989 Jul;48(1):170–173. doi: 10.1097/00007890-198907000-00046. [DOI] [PubMed] [Google Scholar]
  32. Zamvil S. S., Nelson P. A., Mitchell D. J., Knobler R. L., Fritz R. B., Steinman L. Encephalitogenic T cell clones specific for myelin basic protein. An unusual bias in antigen recognition. J Exp Med. 1985 Dec 1;162(6):2107–2124. doi: 10.1084/jem.162.6.2107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Zamvil S., Nelson P., Trotter J., Mitchell D., Knobler R., Fritz R., Steinman L. T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. 1985 Sep 26-Oct 2Nature. 317(6035):355–358. doi: 10.1038/317355a0. [DOI] [PubMed] [Google Scholar]
  34. Zhang J. W., Chou C. H., Hashim G., Medaer R., Raus J. C. Preferential peptide specificity and HLA restriction of myelin basic protein-specific T cell clones derived from MS patients. Cell Immunol. 1990 Aug;129(1):189–198. doi: 10.1016/0008-8749(90)90197-y. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES