Inhibition of the progression of multiple sclerosis by linomide is associated with upregulation of CD4+/CD45RA+ cells and downregulation of CD4+/CD45RO+ cells

Clinical Immunology and Immunopathology

Volumn 85, Issue 2, 1997, Pages 202-209

  Lehmann, Dan ^a,b   Karussis, Dimitrios ^a   Mizrachi Koll, Rachel ^a   Linde, Anders S ^a   Abramsky, Oded ^a  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^b PFIZER INC   (United States)

Author keywords

CD45RA RO; Immunomodulation; Linomide; Multiple sclerosis

Indexed keywords

CD14 ANTIGEN; CD16 ANTIGEN; CD19 ANTIGEN; CD3 ANTIGEN; CD4 ANTIGEN; CD45 ANTIGEN; CD5 ANTIGEN; CD8 ANTIGEN; LYMPHOCYTE SURFACE MARKER; ROQUINIMEX;

ADULT; ARTICLE; AUTOIMMUNITY; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DOWN REGULATION; FEMALE; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IMMUNOMODULATION; LEUKOCYTE COUNT; LYMPHOCYTE SUBPOPULATION; MALE; MEMORY CELL; MULTIPLE SCLEROSIS; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; T LYMPHOCYTE;

EID: 0030731322     PISSN: 00901229     EISSN: None     Source Type: Journal    
DOI: 10.1006/clin.1997.4444     Document Type: Article

References (89)

1. Hafler, D. A., and Weiner, H. L., MS: A CNS and systemic autoimmune disease. Immunol. Today 10, 104-107, 1989.
2. Raine, C. S., The Dale E. McFarlin Memorial Lecture: The immunology of the multiple sclerosis lesion. Ann. Neural, 36(suppl.), S61-S72, 1994.
3. Myers, L. W., Fahey, J. L., Moody, D. J., et al., Cyclophosphamide "pulses" in chronic progressive multiple sclerosis: A preliminary clinical trial. Arch. Neural. 44, 829-832, 1987.
4. Likosky, W. H., Experience with cyclophosphamide in multiple sclerosis: The cons. Neurology 1988.
5. Hauser, S. L., Dawson, D. M., and Lehrich, J. R., Intensive immune suppression in progressive multiple sclerosis: A randomized three arm study of high-dose intravenous cyclophosphamide, plasma exchange and ACTH. N. Engl. J. Med. 308, 173, 1983.
6. Group, T. M. S. S., Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: A randomized, double-blinded, placebo-controlled clinical trial. Ann. Neurol. 27,591-605, 1990.
7. Kappos, L., Patzold, U., Dommasch, D., et al., Cyclosporine vs azathioprine in the long-term treatment of multiple sclerosis-results of the German multicenter study. Ann. Neurol. 23, 56-63, 1988.
8. Durelli, L., and Bergamini, L., Multiple sclerosis. II. A critical assessment of immunotherapy. Riv. Neurol. 59, 191-201, 1989.
9. Milligan, N. M., Newcombe, R., and Compston, D. A. S., A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis. 1. Clinical effects. J. Neurol. Neurosurg. Psych. 50, 511-516, 1987.
10. Cohen, I. R., and Young, D. B., Autoimmunity, microbial immu-nity and the immunological homunculus. Immunol. Today 12, 105-110, 1991.
11. Lieder, O., Reshef, T., Berauud, B., Ben-Nun, A., and Cohen, I. R., Anti-idiotypic network induced by T cell vaccination against experimental autoimmune encephalomyelitis. Science 239, 181-183, 1988.
12. Balashov, K. E., Khoury, S. J., Hafler, D. A., and Weiner, H. L., Inhibition of T cell responses by activated human CD8+ T cells is mediated by interferon-gamma and is defective in chronic progressive multiple sclerosis. J. Clin. Invest. 95,2711-2719,1995.
13. Bongioanni, P., Fioretti, G., Vanacore, R., et al., Lymphocyte subsets in multiple sclerosis: A study with two-colour fluorescence analysis. J. Neural. Sei. 139, 71-77, 1996.
14. Calopa, M., Bas, J., Mestre, M., Arbizu, T., Pères, J., and Buendia, E., T cell subsets in multiple sclerosis: A serial study. Acta Neural. Scand. 92, 361-368, 1995.
15. Chofflon, M., Weiner, H. L., and Hafler, D. A., Loss of functional suppression is linked to decreases in circulating suppressor-inducer (CD4+ 2H4+) T cells in multiple sclerosis. Ann. N.Y. Acad. Sci. 540, 330-332, 1988.
16. Chofflon, M., Weiner, H. L., Morimoto, C., and Hafler, D. A., Decrease of suppressor inducer (CD4+2H4+) T cells in multiple sclerosis cerebrospinal fluid [see comments]. Ann. Neural. 25, 494-499, 1989.
17. Crucian, B., Dunne, P., Friedman, H., Ragsdale, R., Pross, S., and Widen, R., Alterations in levels of CD28-/CD8+ suppressor cell precursor and CD45RO+/CD4+ memory T lymphocytes in the peripheral blood of multiple sclerosis patients. Clin. Diagn. Lab. Immunol. 2, 249-252, 1995.
18. Eoli, M., Ferrarini, M., Dufour, A., et al., Presence of T-cell subset abnormalities in newly diagnosed cases of multiple sclerosis and relationship with short-term clinical activity. J. Neural. 240, 79-82, 1993.
19. Ilonen, J., Surcel, H. M., Jagerroos, H., Nurmi, T., and Reunanen, M., T-lymphocyte subsets defined by double immunofluorescence in multiple sclerosis. Acta Neurol. Scand. 81, 128-130, 1990.
20. Macor, S., Porrini, A. M., Giampietro, A., Malatesta, G., and Gambi, D., Multiple sclerosis: An immune system activation disease. Acta Neurol. (Napoli) 13, 590-596, 1991.
21. Porrini, A. M., Gambi, D., and Malatesta, G., Memory and naive CD4+ lymphocytes in multiple sclerosis. J. Neurol. 239, 437-440, 1992.
22. Rose, L. M., Ginsberg, A. H., Rothstein, T. L., Ledbetter, J. A., and Clark, E. A., Selective loss of a subset of T helper cells in active multiple sclerosis. Proc. Natl. Acad. Sei. USA 82, 7389-7393, 1985.
23. Rose, L. M., Ledbetter, J. A., Ginsberg, A. H., Clark, E. A., and Rothstein, T. L., Suppressor-inducer T-cells in multiple sclerosis [letter]. N. Engl. J. Med. 317, 118-119, 1987.
24. Rose, L. M., Ginsberg, A. H., Rothstein, T. L., Ledbetter, J. A., and Clark, E. A., Fluctuations of CD4+ T-cell subsets in remitting-relapsing multiple sclerosis [see comments]. Ann. Neurol. 24, 192-199, 1988.
25. Salmaggi, A., Milanese, C., Eoli, M., La Mantia, L., Nespolo, A., and Dufour, A., Immunological monitoring and clinical evaluation in cyclophosphamide-treated progressive multiple sclerosis patients. Int. J. Neurosci. 76, 305-312, 1994.
26. Selmaj, K, Plater-Zyberk, C., Rockett, K. A., et al., Multiple sclerosis: Increased expression of interleukin-2 receptors on lymphocytes. Neurology 36, 1392-1395, 1986.
27. Sohen, S., Romain, P. L., Rothstein, D. M., et al., Phenotypic abnormalities in CD8+ T lymphocyte subsets in patients with rheumatoid arthritis. J. Rheumatol. 18, 1649-1654, 1991.
28. Strauss, K., Hulstaert, F., Deneys, V., et al., The immune profile of multiple sclerosis: T-lymphocyte effects predominate over all other factors in cyclophosphamide-treated patients. J. Neuroimmunol. 63, 133-142, 1995.
29. Zaffaroni, M., Rossini, S., Ghezzi, A., Parma, R., and Cazzullo, C. L., Decrease of CD4+CD45+ T-cells in chronic-progressive multiple sclerosis. J. Neural. 237, 1-4, 1990.
30. Zaffaroni, M., Gallo, L., Ghezzi, A., and Cazzullo, C. L., CD4+ lymphocyte subsets in the cerebrospinal fluid of multiple sclerosis and non-inflammatory neurological diseases. J. Neurol. 238, 209-211, 1991.
31. Afeltra, A., Paggi, A., Ferri, G. M., et al., CD5+ B lymphocytes and CD4+ CD45RA+ T cells in Graves' disease. Endocr. Res. 19, 73-85, 1993.
32. Dahle, C., Vrethem, M., and Ernerudh, J., T lymphocyte subset abnormalities in peripheral blood from patients with the Guillain-Barre syndrome. J. Neuroimmunol. 53, 219-225, 1994.
33. Mokhtarian, F., Shi, Y., Shirazian, D., Morgante, L., Miller, A., and Grob, D., Defective production of anti-inflammatory cytokine, TGF-beta by T cell lines of patients with active multiple sclerosis. J. Immunol. 152, 6003-6010, 1994.
34. Scott, T. F., McKolanis, J., Rothfus, W., and Cottington, E., Lymphocyte subsets in relapsing-remitting multiple sclerosis: A longitudinal study of B lymphocytes and T lymphocytes. Neurol. Res. 16, 385-388, 1994.
35. Jamin, C., Lamour, A., Pennee, Y. L., Hirn, M., Le Goff, P., and Youinou, P., Expression of CDS and CD72 on T and B cell subsets in rheumatoid arthritis and Sjogren's syndrome. Clin. Exp. Immunol. 92, 245-250, 1993.
36. Iwase, O., Aoki, I., Kuriyama, Y., et al., Analysis of T cell subsets in autoimmune hemolytic anemia patients. Rinsho Ketsueki 36, 1-5, 1995.
37. Merrill, J., Jondal, M., Seeley, J., Ullberg, M., and Siden, A., Decreased NK killing in patients with MS: An analysis on the level of the single effector cell in peripheral blood and cerebrospinal fluid in relation to the activity of the disease. Clin. Exp. Immunol. 47, 419-430, 1982.
38. Neighbour, P. A., Grayzel, A. I., and Miller, A. E., Endogenous and interferon-augmented NK cell activity of human peripheral blood mononuclear cells in vitro: Studies of patients with multiple sclerosis, systemic lupus erythematosus or rheumatoid arthritis. Clin. Exp. Immunol. 49, 11-21, 1982.
39. Thomson, A. W., Woo, J., Lemster, B., et al., Incidence of CD4+ IL-2R alpha+ and CD4+ CD45RA+ T-cells in progressive multiple sclerosis and the influence of short-term (3 months) FK 506 therapy. Ann. N.Y. Acad. Sei. 696, 245-249, 1993.
40. Rep, M. H., Hintzen, R. Q., Polman, C. H., and van Lier, R. A., Functional defects in peripheral blood T cells of multiple sclerosis patients: Diminished in vitro responsiveness in accessory cell dependent activation systems. J. Neuroimmunol. 52, 139-146, 1994.
41. Group, T. I. M. S. S., Interferon beta-lb is effective in relapsingremitting multiple sclerosis. I. Clinical results of a multicenter, rendomized, double-blind, placebo-controlled trial. Neurology 43, 655-661, 1993.
42. Group, T. I. M. S. S., Interferon beta-lb in the treatment of multiple sclerosis: Final outcome of the randomized controlled trial-The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group. Neurology 45, 1277-1285, 1995.
43. Jacobs, L. D., Cookfair, D. L., Rudick, R. A., et al., Intramuscular Interferon beta-la for disease progression in relapsing multiple sclerosis. Ann. Neurol. 39, 285-294, 1996.
44. Johnson, K. P., Brooks, B. R., Cohen, J. A., et al., Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: Results of a phase III multicenter, double-blind placebo-controlled trial - The Copolymer 1 Multiple Sclerosis Study Group [see comments]. Neurology 45, 1268-1276, 1995.
45. Dore, D. P., Washington, R., and Dragovic, L., Expression of endothelial cell activation antigens in microvessels from patients with multiple sclerosis. Adv. Exp. Med. Biol. 331, 243-248, 1993.
46. Sharief, M. K, Noori, M. A., Ciardi, M., Cirelli, A., and Thompson, E. J., Increased levels of circulating ICAM-1 in serum and cerebrospinal fluid of patients with active multiple sclerosis: Correlation with TNF-alpha and blood-brain barrier damage. J. Neuroimmunol. 43, 15-21, 1993.
47. Svenningsson, A., Hansson, G. K, Andersen, O., Andersson, R., Patarroyo, M., and Stemme, S., Adhesion molecule expression on cerebrospinal fluid T lymphocytes: Evidence for common recruitment mechanisms in multiple sclerosis, aseptic meningitis, and normal controls. Ann. Neural. 34, 155-161, 1993.
48. Tsukada, N., Miyagi, K, Matsuda, M., and Yanagisawa, N., Increased levels of circulating intercellular adhesion molecule-1 in multiple sclerosis and human T-lymphotropic virus type I-associated myelopathy. Ann. Neural. 33, 646-649, 1993.
49. Tsukada, N., Matsuda, M., Miyagi, K., and Yanagisawa, N., Increased levels of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor receptor in the cerebrospinal fluid of patients with multiple sclerosis. Neurology 43, 2679-2682, 1993.
50. Tsukada, N., Matsuda, M., Miyagi, K, and Yanagisawa, N., Adhesion of cerebral endothelial cells to lymphocytes from patients with multiple sclerosis. Autoimmunity 14, 329-333, 1993.
51. Tsukada, N., Matsuda, M., Miyagi, K, and Yanagisawa, N., In vitro intercellular adhesion molecule-1 expression on brain endothelial cells in multiple sclerosis. J. Neuroimmunol. 49, 181-187, 1994.
52. Washington, R., Burton, J., Todd, R. R., Newman, W., Dragovic, L., and Dore, D. P., Expression of immunologically relevant endothelial cell activation antigens on isolated central nervous system microvessels from patients with multiple sclerosis. Ann. Neurol. 35, 89-97, 1994.
53. Wilcox, C. E., Ward, A. M., Evans, A., Baker, D., Rothlein, R., and Turk, J. L., Endothelial cell expression of the intercellular adhesion molecule-1 (ICAM-1) in the central nervous system of guinea pigs during acute and chronic relapsing experimental allergic encephalomyelitis. J. Neuroimmunol. 30, 43-51, 1990.
54. Clement, L. T., Vink, P. E., and Bradley, G. E., Novel immunoregulatory functions of phenotypically distinct subpopulations of CD4+ cells in the human neonate. J. Immunol. 145, 102-108, 1990.
55. Clement, L. T., Functional and phenotypic properties of 'naive' and 'memory" CD4+ T cells in the human. Immunol. Res. 10, 189-195, 1991.
56. Clement, L. T., Isoforms of the CD45 common leukocyte antigen family: Markers for human T-cell differentiation. J. Clin. Immunol. 12, 1-10, 1992.
57. Sanders, M. E., Makgoba, M. W., and Shaw, S., Human naive and memory T cells: Reinterpretation of helper-inducer and suppressor-inducer subsets. Immunol. Today 9, 195-199, 1988.
58. Bradley, L. M., Duncan, D. D., Tonkonogy, S., and Swin, S. L., Characterization of antigen-specific CD4+ effector T cells in vivo: Immunization results in a transient population of MEL-14-, CD45RB-helper cells that secrete interleukine 2 (IL-2) IL-3, IL-4 and interferon gamma. J. Exp. Med. 174, 547-559, 1991.
59. Jensen, G. S., Andrews, E. J., Mant, M. J., Vergidis, R., Ledbetter, J. A., and Pilarski, L. M., Transitions in CD45 isoform expression indicate continuous differentiation of a monoclonal CD5+ CD11b+ B lineage in Waldenstrom's macroglobulinemia. Am. J. Hematol. 37, 20-30, 1991.
60. Qin, Y., Van Den Noort, S., Kurt, J., and Gupta, S., Dual expression of CD45RA and CD45RO isoforms on myelin basic proteinspecific CD4+ T-cell lines in multiple sclerosis. J. Clin. Immunol. 13, 152-161, 1993.
61. Khoury, S. J., Guttmann, C., Ahn, S., et al., Correlation between MRI and immunologie studies in MS patients. Neurology 43, S182, 1993.
62. Rothstein, D. M., Yamada, A., Schlossman, S. F., and Morimoto, C., Cyclic regulation of CD45 isoform expression in a long term human CD4+CD45RA+ T cell line. J. Immunol. 146, 1175-1183, 1991.
63. Yamada, A., Kaneyuki, T., Kara, A., Rothstein, D. M., and Yokoyama, M. M., CD45 isoform expression on human neonatal T cells: Expression and turnover of CD45 isoforms on neonatal versus adult T cells after activation. Cell. Immunol. 142, 114-124, 1992.
64. Karussis, D. M., Lehmann, D., Slavin, S., et al., Inhibition of acute experimental autoimmune encephalomyelitis by the synthetic immunomodulator linomide. Ann. Neural. 34, 654-660, 1993.
65. Karussis, D. M., Slavin, S., Lehmann, D., et al., Successful treatment of chronic-relapsing experimental autoimmune encephalomyelitis with linomide (LS-2616), a synthetic immunomodulator. Proc. Natl. Acad. Sci. USA 90, 6400-6404, 1993.
66. Karussis, D. M., Meiner, Z., Lehmann, D., et al., Treatment of secondary progressive multiple sclerosis with the immunomodulator linomide: A pilot double-blind placebo controlled study with monthly MRI evaluation. Neurology 47, 341-346, 1996.
67. Poser, C. M., Paty, D. W., Scheinberg, L., et al., New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann. Neurol. 13, 227-231, 1983.
68. Kurtzke, J. F., Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33, 1444-1452, 1983.
69. Smith, M. E., Stone, L. A., Albert, P. A., et al., Clinical worsening in MS associated with increased frequency and area ofgadopentate dimeglumine enhancing MRI lesions. Ann. Neural. 33, 480-489, 1993.
70. Frank, J. A., Stone, L. A., Smith, M. E., Albert, P. S., Maloni, H., and McFarland, H. F., Serial contrast-enhanced magnetic resonance imaging in patients with early relapsing-remitting multiple sclerosis: Implications for treatment trials. Ann. Neuroi 36, S86-S90, 1994.
71. Pilarski, L. M., Yacyshyn, B. R., Jensen, G. S., Pruski, E., and Pabst, H. F., Beta l integrin (CD29) expression on human postnatal T cell subsets defined by selective CD45 isoform expression. J. Immunol. 147, 830-837, 1991.
72. Iwase, O., Ohosumi, A., Fujieda, H., et al., A case of Evans' syndrome in which CD4+CD45RA+ cells markedly decreased in its active phase. Rinsho Ketsueki 34, 859-864, 1993.
73. Gordon, C., Matthews, N., Schlesinger, B. C., et al., Active sys- s temic lupus erythematosus is associated with the recruitment of naive/resting T cells. Br. J. Rheumatol. 35, 226-230, 1996.
74. Shah, P. D., Gilbertson, S. M., and Rowley, D. A., Dendritic cells that have interacted with antigen are targets for NK cells. J. Exp. Med. 162, 625-636, 1985.
75. Dighiero, G., Hart, S., Lim, A., Borche, L., Levy, R., and Miller, R. A., Autoantibody activity of immunoglobulins isolated from B-cell follicular lymphomas. Blood 78, 581-585, 1991.
76. Inghirami, G., Foitl, D. R., Sabichi, A., Zhu, B. Y., and Knowles, D. M., Autoantibody-associated cross-reactive idiotype-bearing human B lymphocytes: distribution and characterization, including Ig VH gene and CDS antigen expression. Blood 78, 1503-1515, 1991.
77. Jasin, H. E., The relationship between circulating CD5+ B lymphocytes and in vitro autoantibody synthesis in normal individuals. Cell. Immunol. 136, 133-141, 1991.
78. Kipps, T. J., and Duffy, S. F., Relationship of the CD5 B cell to human tonsillar lymphocytes that express autoantibody-associated cross-reactive idiotypes. J. Clin. Invest. 87, 2087-2096, 1991.
79. Ansar, A. S., Dauphinee, M. J., Montoya, A. L, and Talal, N., Estrogen induces normal murine CD5+ B cells to produce autoantibodies. J. Immunol. 142, 2647-2653, 1989.
80. Mackenzie, L. E., Youinou, P. Y., Hicks, R., Yuksel, B., Mageed, R. A., and Lydyard, P. M., Auto- and polyreactivity of IgM from CD5+ and CDS- cord blood B cells. Scand. J. Immunol. 33, 329-335, 1991.
81. Abramsky, O., Karussis, D., Mizrachi-Koll, R., and Lehmann, D., Inoculation of BCL1 lymphoma cells into CSJL/J mice inhibits acute experimental autoimmune encephalomyelitis. Isr. J. Med. Sei. 30, 1-6, 1994.
82. Arase, H., Arase, N., Nakagawa, K., Good, R. A., and Onoe, K., NK1.1+ CD4+ CDS- thymocytes with specific lymphokine secretion. Eur. J. Immunol. 23, 307-310, 1993.
83. Bendelac, A., Killeen, N., Littman, D. R., and Schwartz, R. H., A subset of CD4+ thymocytes selected by MHC class I molecules. Science 263, 1774-1778, 1994.
84. Emoto, M., Emoto, Y., and Kaufmann, S. H., Interleukin-4-producing CD4+ NK1.1+ TCR alpha/beta intermediate liver lymphocytes are down-regulated by Listeria monocytogenes. Eur. J. Immunol. 25, 3321-3325, 1995.
85. MacDonald, H. R., NK1.1+ T cell receptor-alpha/beta+ cells: New clues to their origin, specificity, and function. J. Exp. Med. 182, 633-638, 1995.
86. pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3. J. Exp. Med. 179, 1285-1295, 1994.
87. Forsthuber, T., Yip, H. C., and Lehmann, P. V., Induction of TH1 and TH2 immunity in neonatal mice [see comments]. Science 271, 1728-1730, 1996.
88. Ridge, J. P., Fuchs, E. J., and Matzinger, P., Neonatal tolerance revisited: Turning on newborn T cells with dendritic cells [see comments]. Science 271, 1723-1726, 1996.
89. Wood, K. J., New concepts in tolerance. Clin. Transplant. 10, 93-99, 1996.