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Dual expression of CD45RA and CD45RO isoforms on myelin basic protein-specific CD4+ T-cell lines in multiple sclerosis

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Abstract

Myelin basic protein (MBP)-specific T-cell lines from patients with multiple sclerosis (MS) and healthy controls were analyzed for the expression of CD45 isoforms and adhesion molecules. In the multiple sclerosis group, 22 of 24 MBP-specific T-cell lines were CD4+. Two distinct patterns were observed with regard to CD45 isoform expression. Pattern I showed dual expression of CD45 isoforms (CD4+CD45RA+CD45RO+CD29+) and Pattern II included cells with a single CD45 isoform (CD4+CD45RA−CD45RO+CD29+). All 10 cell lines from healthy controls were CD4+ and displayed Pattern II (CD4+CD45RA−CD45RO+CD29+). The dual expression of CD45 isoform in T-cell lines from MS was stable, did not represent a transition stage from CD45RA to CD45RO, and was cell-cycle independent. All cell lines from MS and controls expressed increased levels of LFA-1 (CD11a), LFA-2 (CD2), LFA-3 (CD58), ICAM-1 (CD54), and VLA-4 (CDw49d). These data show the presence of unique MBP-specific T cells (CD4+CD45RA+CD45RO+CD29+) that might play a role in the pathogenesis of MS.

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References

  1. Wucherpfennig KW, Weiner HL, Hafler DA: T cell recognition of myelin basic protein. Immunol Today 12:277–282, 1991

    Google Scholar 

  2. Martin R, Howell MD, Jaraquemada D, Flerlage M, Richert J, Brostoff S, Long EO, McFarlin DE, McFarland HF: A myelin basic protein peptide is recognized by cytotoxic T cells in the context of four HLA-DR type associated with multiple sclerosis. J Exp Med 173:19–24, 1991

    Google Scholar 

  3. Ben-Nun A, Liblau RS, Cohen L, Lehmann D, Tournier-Lasserve E, Rosenzweig A, Jingwu Z, Raus J, Bach MA: Restricted T cell receptor Vβ gene usage by myelin basic protein-specific T cell clones in multiple sclerosis. Predominant genes vary in individuals. Proc Natl Acad Sci USA 88:2466–2470, 1991

    Google Scholar 

  4. Kotzin B, Karuturi S, Chou YK, Lafferty J, Forrester JM, Better M, Nedwin GE, Offner H, Vandenbank AA: Preferential T cell receptor β-chain variable gene use in myelin basic protein-reactive T-cell clones from patients with multiple sclerosis. Proc Natl Acad Sci USA 88:9161–9165, 1991

    Google Scholar 

  5. Ota K, Matsui M, Milford EL, Mackin GA, Weiner HL, Hafler DA: T cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 346:183–187, 1991

    Google Scholar 

  6. Martin R, Jaraquemada D, Flerlage M, Richert J, Whitaker J, Long EO, McFarlin DE, McFarland HF: Fine specificity and HLA restriction of myelin basic protein-specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals. J Immunol 145:540–548, 1990

    Google Scholar 

  7. Chou YK, Vainiene M, Whitham R, Bourdette D, Chou CH-J, Hashim G, Offner H, Vandenbark AA: Response of human T lymphocyte lines to myelin basic protein: Association of dominant epitopes with HLA class II restriction molecules. J Neurosci Res 23:207–216, 1989

    Google Scholar 

  8. Zamvil SS, Steinman L: The T lymphocytes in experimental allergic encephalomyelitis. Annu Rev Immunol 8:579–621, 1990

    Google Scholar 

  9. Alleretta M, Nicklas JA, Sriram S, Albertini RJ: T cell responsiveness to myelin basic protein in patients with multiple sclerosis. Science 247:718–721, 1990

    Google Scholar 

  10. Traugott U, Reinharz EL, Raine CS: Multiple sclerosis: Distribution of T cell subsets with active chronic lesions. Science 219:308–310, 1983

    Google Scholar 

  11. Sanders ME, Makgoba MW, Shaw S: Human naive and memory T cells: Reinterpretation of helper-inducer and suppressor-inducer subsets. Immunol Today 9:195–199, 1988

    Google Scholar 

  12. Clement LT: Isoforms of the CD45 common leukocyte antigen family: Markers for human T cell differentiation. J Clin Immunol 12:1–10, 1992

    Google Scholar 

  13. Thomas ML: The leucocyte common antigen family. Annu Rev Immunol 7:339–369, 1989

    Google Scholar 

  14. Morimoto C, Letvin NC, Boyd AW, Hagen M, Brown HM, Kornacki MM, Schlossman SF: The isolation and characterization of the human suppressor-inducer T cell subset. J Immunol 134:3762–3769, 1989

    Google Scholar 

  15. Janossy G, Campana D, Akbar A: Kinetics of T lymphocyte development.In Cell Kinetics of the Inflammatory Reaction, OH Iverson (ed). New York, Springer-Verlag, 1989, pp 59–99

    Google Scholar 

  16. Rose LM, Ginsberg AH, Rothstein DL, Ledbetter JA, Clark EA: Selected loss of a subset of T helper cells in active multiple sclerosis. Proc Natl Acad Sci USA 82:7389–7393, 1985

    Google Scholar 

  17. Morimoto C, Hafler DA, Weiner DL, Letvin NL, Hagan M, Daley J, Schlossman SF: Selective loss of the suppressor-inducer T cell subset in progressive multiple sclerosis: Analysis with anti-2H4 monoclonal antibody. N Engl J Med 316:67–72, 1987

    Google Scholar 

  18. Sobel RA, Hafler DA, Castro EE, Morimoto C, Weiner HL: The 2H4 (CD45R) antigen is selectively decreased in multiple sclerosis lesion. J Immunol 140:2210–2214, 1988

    Google Scholar 

  19. Springer TA: Adhesion receptors of the immune system. Nature 346:425–434, 1990

    Google Scholar 

  20. McDonald WI, Halliday AM: Diagnosis and classification of multiple sclerosis. Br Med Bull 33:4–8, 1977

    Google Scholar 

  21. Eylar EH, Kniskern PJ, Jackson JJ: Myelin basic proteins. Methods Enzymol 32:323–341, 1974

    Google Scholar 

  22. Taylor IW: A rapid single step staining technique for DNA analysis by flow microfluorometry. J Histochem Cytochem 28:1021–1024, 1990

    Google Scholar 

  23. Akbar AN, Terry L, Timms A, Beverley PCL, Jenossy G: Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol 140:2171–2178, 1988

    Google Scholar 

  24. Rothstein DM, Yamada A, Schlossman SF, Morimoto C: Cyclic regulation of CD45 isoform expression in a long term human CD4+CD45RA+ T cell line. J Immunol 146:1175–1183, 1991

    Google Scholar 

  25. LaSalle J, Hafler DA: The coexpression of CD45RA and CD45RO isoforms on T cells during the S/G2/M stages of cell cycle. Cell Immunol 138:197–206, 1991

    Google Scholar 

  26. Traugott U, Reinherz EL, Raine CS: Multiple sclerosis: Distribution of T cells, T cell-subsets and Ia positive macrophages in lesion of different ages. J Neuroimmunol 4:201–221, 1983

    Google Scholar 

  27. Waksman BH: Autoimmunity in demylinating diseases. Ann NY Acad Sci 540:13–24, 1988

    Google Scholar 

  28. Clark EA, Ledbetter JA: A leukocyte cell surface antigen: CD45 (LCA, T200) is a protein tyrosine phosphatase. Immunol Today 10:225–278, 1989

    Google Scholar 

  29. Hirohata S, Lipsky P: T cell regulation of human B cell proliferation and differentiation. J Immunol 142:2597–2607, 1989

    Google Scholar 

  30. Rothstein DM, Soshen S, Schlossman SF, Morimoto C: CD4+CD45RA− subset in man maintain distinct function and CD45RA expression persists on a subpopulation of CD45RA+ cells after activation with con A. Cell Immunol 129:449–467, 1990

    Google Scholar 

  31. Bell EB, Sparshott SM: Interconversion of CD45R subset of CD4+ T cells in vivo. Nature 348:163–166, 1990

    Google Scholar 

  32. Selmaj KW, Raine CS: Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 23:339–346, 1988

    Google Scholar 

  33. Hofman FM, Hilton DR, Johnson K, Merril JE: Tumor necrosis factor identified in multiple sclerosis brain. J Exp Med 170:607–612, 1989

    Google Scholar 

  34. Maimone D, Gregory S, Arnason BG, Reder AT: Cytokine levels in the cerebrospinal fluid and serum of patients in multiple sclerosis. J Neuroimmunol 32:67–74, 1991

    Google Scholar 

  35. Sharief MK, Hentges R: Association between tumor necrosis factor-α and disease progression in patients with multiple sclerosis. N Engl J Med 325:467–472, 1991

    Google Scholar 

  36. Selmaj K, Raine CS, Cannella B, Brosnan CF: Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. J Clin Invest 87:949–954, 1991

    Google Scholar 

  37. Mossman T, Cherwinski H, Bond M-W,et al.: Two types of murine helper T cell clones. I. Definition according to profile of lymphokine activities and secreted proteins. J Immunol 136:2348–2357, 1986

    Google Scholar 

  38. Romagnani S: Human Th1 and Th2 subsets doubt no more. Immunol Today 12:256–257, 1991

    Google Scholar 

  39. Salgame P, Abrams JS, Clayberger C, Goldstein H, Convit J, Modlin RL, Bloom BR: Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science 254:279–282, 1991

    Google Scholar 

  40. Yamamura M, Uyemura K, Deans RJ, Weinberg K, Rea TH, Bloom BR, Modlin RL: Defining protective responses to pathogens: Cytokine profiles in leprosy lesions. Science 254:277–279, 1991

    Google Scholar 

  41. Albelda SM, Buck CA: Integrins and other cell adhesion molecules. FASEB J 4:2868–2880, 1990

    Google Scholar 

  42. Shimizu Y, van Seventer GA, Horgan KJ, Shaw S: Role of adhesion molecules in T-cell recognition: Fundamental similarities between four integrins on resting T cells (LFA-1, VLA-4, VLA-5, VLA-6) in expression, binding, and costimulation. Immunol Rev 114:109–143, 1990

    Google Scholar 

  43. Sanders ME, Makgoba MW, Sharrow SO, Stephany D, Springer TA, Young HA, Shaw S: Human memory T cells express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL 1, CDw29, and pgp-1) and have enhanced IFNγ production. J Immunol 140:1401–1407, 1988

    Google Scholar 

  44. Pober JS, Gimbrone MA Jr, Lapierre LA, Mendrick DL, Fiers W, Rothlein R, Springer TA: Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol 137:1893–1896, 1986

    Google Scholar 

  45. Pober JS, Lapierre LA, Stolpen AH, Brock TA, Springer TA, Fiers W, Bevilacqua MP, Mendrick DL, Gimbrone MA Jr: Activation of cultured human endothelial cells by recombinant lymphotoxin: Comparison with tumor necrosis factor and interleukin 1 species. J Immunol 138:3319–3324, 1987

    Google Scholar 

  46. Frohman EM, Frohman TC, Dustin ML, Vayuvegula B, Choi B, van den Noort S, Gupta S: The induction of ICAM-1 on human fetal astrocytes by IFNγ, TNFα, LT, and IL-1. J Neuroimmunol 23:117–124, 1989

    Google Scholar 

  47. Dustin ML, Springer TA: Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of the at least three mechanisms for lymphocyte adhesion to cultured endothelial cells. J Cell Biol 107:321–331, 1988

    Google Scholar 

  48. Hemler ME, Elices MJ, Parker C, Takada Y: Structure of integrin VLA-4 and its cell-cell and cell-matrix adhesion function. Immunol Rev 114:45–65, 1990

    Google Scholar 

  49. Hemler ME, Takada Y, Elices M, Croose C: Structure and function for adhesion receptors VLA-2 and VLA-4: Comparison to other members of the integrin superfamily.In Leukocyte Adhesion Molecules, TA Springer, DA Anderson, AS Rosenthal, Rothlein (eds). New York, Springer-Verlag, 1989, pp 44–57

    Google Scholar 

  50. Hemler ME: Adhesive protein receptors on hematopoietic cells. Immunol Today 9:109–113, 1988

    Google Scholar 

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Qin, Y., van den Noort, S., Kurt, J. et al. Dual expression of CD45RA and CD45RO isoforms on myelin basic protein-specific CD4+ T-cell lines in multiple sclerosis. J Clin Immunol 13, 152–161 (1993). https://doi.org/10.1007/BF00919272

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