Expanded TCR Vβ subsets of CD8+ T-cells in late-onset myasthenia gravis: Novel parallels with thymoma patients

Journal of Neuroimmunology

Volumn 216, Issue 1-2, 2009, Pages 85-91

  Tackenberg, B ^a   Schlegel, K ^a   Happel, M ^a   Eienbroker C ^a   Gellert, K ^b   Oertel, W H ^a   Meager, A ^c   Willcox, N ^d   Sommer, N ^a,e  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

^b SANA KLINIKUM OFFENBACH   (Germany)

^c NATIONAL INSTITUTE FOR BIOLOGICAL STANDARDS AND CONTROL   (United Kingdom)

^d UNIVERSITY OF OXFORD   (United Kingdom)

^e Christophsbad   (Germany)

Author keywords

Anti IFN 2; Anti IL 12; CD8+ TCR V beta expansions; Cytomegalovirus; Late onset myasthenia gravis; Recent thymic emigrants

Indexed keywords

ALPHA2 INTERFERON; CD45RA ANTIGEN; IMMUNOGLOBULIN G ANTIBODY; INTERLEUKIN 12; L SELECTIN; T LYMPHOCYTE RECEPTOR; T LYMPHOCYTE RECEPTOR VBETA; UNCLASSIFIED DRUG; AUTOANTIBODY; CD45 ANTIGEN; LYMPHOCYTE ANTIGEN RECEPTOR; RECOMBINANT GAMMA INTERFERON;

ADULT; ANTIBODY RESPONSE; ARTICLE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; CYTOMEGALOVIRUS; FEMALE; HUMAN; IMMUNOPHENOTYPING; MAJOR CLINICAL STUDY; MALE; MYASTHENIA GRAVIS; PRIORITY JOURNAL; THYMOMA; AGED; BLOOD; DIFFERENTIAL DIAGNOSIS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; METABOLISM; MIDDLE AGED; ONSET AGE; PATHOPHYSIOLOGY; PHYSIOLOGY;

ADULT; AGE OF ONSET; AGED; ANTIGENS, CD45; AUTOANTIBODIES; CD8-POSITIVE T-LYMPHOCYTES; CYTOMEGALOVIRUS; DIAGNOSIS, DIFFERENTIAL; FEMALE; HUMANS; IMMUNOPHENOTYPING; INTERFERON-GAMMA, RECOMBINANT; INTERLEUKIN-12; L-SELECTIN; LYMPHOCYTE ACTIVATION; MALE; MIDDLE AGED; MYASTHENIA GRAVIS; RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA; THYMOMA;

EID: 71749086824     PISSN: 01655728     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jneuroim.2009.08.018     Document Type: Article

References (52)

1. Aarli J.A. Myasthenia gravis in the elderly: is it different?. Ann. N. Y. Acad. Sci. 1132 (2008) 238-243
2. Aarli J.A., Stefansson K., Marton L.S., and Wollmann R.L. Patients with myasthenia gravis and thymoma have in their sera IgG autoantibodies against titin. Clin. Exp. Immunol. 82 (1990) 284-288
3. Aarli J.A., Romi F., Skeie G.O., and Gilhus N.E. Myasthenia gravis in individuals over 40. Ann. N. Y. Acad. Sci. 998 (2003) 424-431
4. Almeida A.R., Rocha B., Freitas A.A., and Tanchot C. Homeostasis of T cell numbers: from thymus production to peripheral compartmentalization and the indexation of regulatory T cells. Semin. Immunol. 17 (2005) 239-249
5. Bains I., Antia R., Callard R., and Yates A.J. Quantifying the development of the peripheral naive CD4+ T cell pool in humans. Blood 113 (2009) 5480-5487
6. Buckley C., Douek D., Newsom-Davis J., Vincent A., and Willcox N. Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis. Ann. Neurol. 50 (2001) 64-72
7. Buckley C., Newsom-Davis J., Willcox N., and Vincent A. Do titin and cytokine antibodies in MG patients predict thymoma or thymoma recurrence?. Neurology 57 (2001) 1579-1582
8. Chen G., Marx A., Wen-Hu C., Yong J., Puppe B., Stroebel P., and Mueller-Hermelink H.K. New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China. Cancer 95 (2002) 420-429
9. Chidrawar S., Khan N., Wei W., McLarnon A., Smith N., Nayak L., and Moss P. Cytomegalovirus-seropositivity has a profound influence on the magnitude of major lymphoid subsets within healthy individuals. Clin. Exp. Immunol. 155 (2009) 423-432
10. Clambey E.T., van Dyk L.F., Kappeler J.W., and Marrack P. Non-malignant clonal expansions of CD8+ memory T cells in aged individuals. Immunol. Rev. 205 (2005) 170-189
11. Compston D.A., Vincent A., Newsom-Davis J., and Batchelor J.R. Clinical, pathological, HLA antigen and immunological evidence for disease heterogeneity in myasthenia gravis. Brain 103 (1980) 579-601
12. Friese M.A., Jakobsen K.B., Friis L., Etzensperger R., Craner M.J., McMahon R.M., Jensen L.T., Huygelen V., Jones E.Y., Bell J.I., and Fugger L. Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis. Nat. Med. 14 (2008) 1227-1235
13. Giraud M., Beaurain G., Yamamoto A.M., Eymard B., Tranchant C., Gajdos P., and Garchon H.J. Linkage of HLA to myasthenia gravis and genetic heterogeneity depending on anti-titin antibodies. Neurology 57 (2001) 1555-1560
14. Harley J.B., and James J.A. Epstein-Barr virus infection induces lupus autoimmunity. Bull. N.Y.U. Hosp. Jt. Dis. 64 (2006) 45-50
15. Hoffacker V., Schultz A., Tiesinga J.J., Gold R., Schalke B., Nix W., Kiefer R., Müller-Hermelink H.K., and Marx A. Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease. Blood 96 (2000) 3872-3879
16. Hohlfeld R., Toyka K.V., Heininger K., Grosse-Wilde H., and Kalies I. Autoimmune human T lymphocytes specific for acetylcholine receptor. Nature 310 (1984) 244-246
17. Ishii W., Matsuda M., Hanyuda M., Momose M., Nakayama J., Ehara T., and Ikeda S. Comparison of the histological and immunohistochemical features of the thymus in young- and elderly-onset myasthenia gravis without thymoma. J. Clin. Neurosci. 14 (2007) 110-115
18. Janer M., Cowland A., Picard J., Campbell D., Pontarotti P., Newsom-Davis J., Bunce M., Welsh K., Demaine A., Wilson A.G., and Willcox N. A susceptibility region for myasthenia gravis extending into the HLA-class I sector telomeric to HLA-C. Hum. Immunol. 60 (1999) 909-917
19. Koch S., Larbi A., Ozcelik D., Solana R., Gouttefangeas C., Attig S., Wikby A., Strindhall J., Franceschi C., and Pawelec G. Cytomegalovirus infection: a driving force in human T cell immunosenescence. Ann. N. Y. Acad. Sci. 1114 (2007) 23-35
20. Lünemann J.D., Jelcić I., Roberts S., Lutterotti A., Tackenberg B., Martin R., and Münz C. EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-gamma and IL-2. J. Exp. Med. 205 (2008) 1763-1773
21. Marx A., Müller-Hermelink H.K., and Ströbel P. The role of thymomas in the development of myasthenia gravis. Ann. N. Y. Acad. Sci. 998 (2003) 223-236
22. Meager A., Vincent A., Newsom-Davis J., and Willcox N. Spontaneous neutralising antibodies to interferon-alpha and interleukin-12 in thymoma-associated autoimmune disease. Lancet 350 (1997) 1596-1597
23. Meager A., Wadhwa M., Dilger P., Bird C., Thorpe R., Newsom-Davis J., and Willcox N. Anti-cytokine autoantibodies in autoimmunity: preponderance of neutralizing autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravis. Clin. Exp. Immunol. 132 (2003) 128-136
24. Meager A., Peterson P., and Willcox N. Hypothetical review: thymic aberrations and type-I interferons; attempts to deduce autoimmunizing mechanisms from unexpected clues in monogenic and paraneoplastic syndromes. Clin. Exp. Immunol. 154 (2008) 141-151
25. Mehraein Y., Lennerz C., Ehlhardt S., Remberger K., Ojak A., and Zang K.D. Latent Epstein-Barr virus (EBV) infection and cytomegalovirus (CMV) infection in synovial tissue of autoimmune chronic arthritis determined by RNA- and DNA-in situ hybridization. Mod. Pathol. 17 (2004) 781-789
26. Meloni A., Furcas M., Cetani F., Marcocci C., Falorni A., Perniola R., Pura M., Bøe Wolff A.S., Husebye E.S., Lilic D., Ryan K.R., Gennery A.R., Cant A.J., Abinun M., Spickett G.P., Arkwright P.D., Denning D., Costigan C., Dominguez M., McConnell V., Willcox N., and Meager A. Autoantibodies against type I interferons as an additional diagnostic criterion for autoimmune polyendocrine syndrome type I. J. Clin. Endocrinol. Metab. 93 (2008) 4389-4397
27. Mori M., Kuwabara S., Nemoto Y., Tamura N., and Hattori T. Concomitant chronic inflammatory demyelinating polyneuropathy and myasthenia gravis following cytomegalovirus infection. J. Neurol. Sci. 240 (2006) 103-106
28. Morley J.K., Batliwalla F.M., Hingorani R., and Gregersen P.K. Oligoclonal CD8+ T cells are preferentially expanded in the CD57+ subset. J. Immunol. 154 (1995) 6182-6190
29. Muraro P.A., Jacobsen M., Necker A., Nagle J.W., Gaber R., Sommer N., Oertel W.H., Martin R., and Hemmer B. Rapid identification of local T cell expansion in inflammatory organ diseases by flow cytometric T cell receptor Vbeta analysis. J. Immunol. Methods 246 (2000) 131-143
30. Peacock C.D., and Price P. The role of IL-12 in the control of MCMV is fundamentally different in mice with a retroviral immunodeficiency syndrome (MAIDS). Immunol. Cell. Biol. 77 (1999) 131-138
31. Posnett D.N., Sinha R., Kabak S., and Russo C. Clonal populations of T cells in normal elderly humans: the T cell equivalent to "benign monoclonal gammopathy". J. Exp. Med. 179 (1994) 609-618
32. Schwab R., Szabo P., Manavalan J.S., Weksler M.E., Posnett D.N., Pannetier C., Kourilsky P., and Even J. Expanded CD4+ and CD8+ T cell clones in elderly humans. J. Immunol. 158 (1997) 4493-4499
33. Shiono H., Roxanis I., Zhang W., Sims G.P., Meager A., Jacobson L.W., Liu J.L., Matthews I., Wong Y.L., Bonifati M., Micklem K., Stott D.I., Todd J.A., Beeson D., Vincent A., and Willcox N. Scenarios for autoimmunization of T and B cells in myasthenia gravis. Ann. N. Y. Acad. Sci. 998 (2003) 237-256
34. Sommer N., Willcox N., Harcourt G.C., and Newsom-Davis J. Myasthenic thymus and thymoma are selectively enriched in acetylcholine receptor-reactive T cells. Ann. Neurol. 28 (1990) 312-319
35. Sommer N., Tackenberg B., and Hohlfeld R. The immunopathogenesis of myasthenia gravis. In: Engel A.G. (Ed). Handbook of Clinical Neurology vol. 91 (2008), Elsevier, Amsterdam 169-212
36. Somnier F.E. Myasthenia gravis. Dan. Med. Bull. 43 (1996) 1-10
37. Somnier F.E. Increasing incidence of late-onset anti-AchR antibody-seropositive myasthenia gravis. Neurology 65 (2005) 928-930
38. Somnier F.E., and Engel A. The occurrence of anti-titin antibodies and thymomas: a population survey of MG 1970-1990. Neurology 59 (2002) 92-98
39. Staton T.L., Habtezion A., Winslow M.M., Sato T., Love P.E., and Butcher E.C. CD8+ recent thymic emigrants home to and efficiently repopulate the small intestine epithelium. Nat. Immunol. 7 (2006) 482-488
40. Ströbel P., Moritz R., Leite M.I., Willcox N., Chuang W.Y., Gold R., Nix W., Schalke B., Kiefer R., Müller-Hermelink H.K., Jaretzki III A., Newsom-Davis J., and Marx A. The ageing and myasthenic thymus: a morphometric study validating a standard procedure in the histological workup of thymic specimens. J. Neuroimmunol. 201-202 (2008) 64-73
41. Tackenberg B., Kruth J., Bartholomäus J.E., Schlegel K., Oertel W.H., Willcox N., Hemmer B., and Sommer N. Clonal expansions of CD4+ B helper T cells in autoimmune myasthenia gravis. Eur. J. Immunol. 37 (2007) 849-863
42. Tindall R.S., Cloud R., Luby J., and Rosenberg R.N. Serum antibodies to cytomegalovirus in myasthenia gravis: effects of thymectomy and steroids. Neurology 28 (1978) 273-277
43. Varani S., Cederarv M., Feld S., Tammik C., Frascaroli G., Landini M.P., and Söderberg-Nauclér C. Human cytomegalovirus differentially controls B cell and T cell responses through effects on plasmacytoid dendritic cells. J. Immunol. 179 (2007) 7767-7776
44. Vincent A. Unravelling the pathogenesis of myasthenia gravis. Nat. Rev. Immunol. 2 (2002) 797-804
45. Vincent A., Willcox N., Hill M., Curnow J., MacLennan C., and Beeson D. Determinant spreading and immune responses to acetylcholine receptors in myasthenia gravis. Immunol. Rev. 164 (1998) 157-168
46. Vincent A., Clover L., Buckley C., Grimley Evans J., Rothwell P.M., and Myasthenia Gravis Survey U.K. Evidence of underdiagnosis of myasthenia gravis in older people. J. Neurol. Neurosurg. Psychiatry 74 (2003) 1105-1108
47. Wang Z.Y., Karachunski P.I., Howard Jr. J.F., and Conti-Fine B.M. Myasthenia in SCID mice grafted with myasthenic patient lymphocytes: role of CD4+ and CD8+ cells. Neurology 52 (1999) 484-497
48. Willcox N., Schluep M., Ritter M.A., Schuurman H.J., Newsom-Davis J., and Christensson B. Myasthenic and nonmyasthenic thymoma. An expansion of a minor cortical epithelial cell subset?. Am. J. Pathol. 127 (1987) 447-460
49. Willcox N., Leite M.I., Kadota Y., Jones M., Meager A., Subrahmanyam P., Dasgupta B., Morgan B.P., and Vincent A. Autoimmunizing mechanisms in thymoma and thymus. Ann. N. Y. Acad. Sci. 1132 (2008) 163-173
50. Yamamoto A.M., Gajdos P., Eymard B., Tranchant C., Warter J.M., Gomez L., Bourquin C., Bach J.F., and Garchon H.J. Anti-titin antibodies in myasthenia gravis: tight association with thymoma and heterogeneity of nonthymoma patients. Arch. Neurol. 58 (2001) 885-890
51. Zhang G.X., Ma C.G., Xiao B.G., Bakhiet M., Link H., and Olsson T. Depletion of CD8+ T cells suppresses the development of experimental autoimmune myasthenia gravis in Lewis rats. Eur. J. Immunol. 25 (1995) 1191-1198
52. Zhang G.X., Xiao B.G., Bakhiet M., van der Meide P., Wigzell H., Link H., and Olsson T. Both CD4+ and CD8+ T cells are essential to induce experimental autoimmune myasthenia gravis. J. Exp. Med. 184 (1996) 349-356