Journal of Neuroimmunology
Volume 221, Issue 1 , Pages 73-80 , 15 April 2010

Thymic involution and proliferative T-cell responses in multiple sclerosis

  • Danielle A. Duszczyszyn

      Affiliations

    • Department of Pathology, McGill University, Duff Medical Building, 3775 rue University, Montreal, Quebec, Canada H3A 2B4
    • D. A. D., J. L. W., and D.G. H. contributed equally.
    • ,
  • Julia L. Williams

      Affiliations

    • Department of Pathology, McGill University, Duff Medical Building, 3775 rue University, Montreal, Quebec, Canada H3A 2B4
    • D. A. D., J. L. W., and D.G. H. contributed equally.
    • ,
  • Helen Mason

      Affiliations

    • Department of Pathology, McGill University, Duff Medical Building, 3775 rue University, Montreal, Quebec, Canada H3A 2B4
    • ,
  • Yves Lapierre

      Affiliations

    • Department of Neurology, McGill University, 3601 rue University, Montreal, Quebec, Canada H3A 2B4
    • ,
  • Jack Antel

      Affiliations

    • Department of Neurology, McGill University, 3601 rue University, Montreal, Quebec, Canada H3A 2B4
    • ,
  • David G. Haegert

      Affiliations

    • Department of Pathology, McGill University, Duff Medical Building, 3775 rue University, Montreal, Quebec, Canada H3A 2B4
    • Corresponding Author InformationCorresponding author. Tel.: +1 514 398 5599; fax: +1 514 398 3465.
    • D. A. D., J. L. W., and D.G. H. contributed equally.

Received 27 September 2009 ,Revised 8 January 2010 ,Accepted 8 February 2010.

References 

  1. Almeida AR, Borghans JA, Freitas AA. T cell homeostasis: thymus regeneration and peripheral T cell restoration in mice with a reduced fraction of competent precursors. J. Exp. Med. 2001;194:591–599
  2. Almeida AR, Rocha B, Freitas AA, Tanchot C. Homeostasis of T cell numbers: from thymus production to peripheral compartmentalization and the indexation of regulatory T cells. Semin. Immunol. 2005;17:239–249
  3. Calzascia T, Pellegrini M, Lin A, Garza KM, Elford AR, Shahinian A, et al. CD4 T cells, lymphopenia, and IL-7 in a multistep pathway to autoimmunity. Proc. Natl. Acad. Sci. U. S. A. 2008;105:2999–3004
  4. Datta S, Sarvetnick N. Lymphocyte proliferation in immune-mediated diseases. Trends Immunol. 2009;30:430–438
  5. Dion ML, Poulin JF, Bordi R, Sylvestre M, Corsini R, Kettaf N, et al. HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation. Immunity. 2004;21:757–768
  6. Dion ML, Bordi R, Zeidan J, Asaad R, Boulassel MR, Routy JP, et al. Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection. Blood. 2007;109:2912–2920
  7. Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature. 1998;396:690–695
  8. Dulude G, Cheynier R, Gauchat D, Abdallah A, Kettaf N, Sekaly RP, et al. The magnitude of thymic output is genetically determined through controlled intrathymic precursor T cell proliferation. J. Immunol. 2008;181:7818–7824
  9. Duszczyszyn DA, Beck JD, Antel J, Bar-Or A, Lapierre Y, Gadag V, et al. Altered naive CD4 and CD8 T cell homeostasis in patients with relapsing–remitting multiple sclerosis: thymic versus peripheral (non-thymic) mechanisms. Clin. Exp. Immunol. 2006;143:305–313
  10. Freedman MS, Hughes B, Mikol DD, Bennett R, Cuffel B, Divan V, et al. Efficacy of disease-modifying therapies in relapsing remitting multiple sclerosis: a systematic comparison. Eur. Neurol. 2008;60:1–11
  11. Geenen V, Poulin JF, Dion ML, Martens H, Castermans E, Hansenne I, et al. Quantitation of T cell receptor rearrangement excision circles to estimate thymic function: an important tool for endocrine-immune physiology. J. Endocrinol. 2003;176:305–311
  12. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J. Immunol. 1984;133:1710–1715
  13. Gregory SG, Schmidt S, Seth P, Oksenberg JR, Hart J, Prokop A, et al. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat. Genet. 2007;39:1083–1091
  14. Haas J, Fritsching B, Trubswetter P, Korporal M, Milkova L, Fritz B, et al. Prevalence of newly generated naïve regulatory T cells (Treg) is critical for Treg suppressive function and determines Treg dysfunction in multiple sclerosis. J. Immunol. 2007;179:1322–1330
  15. Haegert DG, Swift FV, Benedikz J. Evidence for a complex role of HLA class II genotypes in susceptibility to multiple sclerosis in Iceland. Neurology. 1996;46:1107–1111
  16. Haegert DG, Galutira D, Murray TJ, O'Connor P, Gadag V. Identical twins discordant for multiple sclerosis have a shift in their T-cell receptor repertoires. Clin. Exp. Immunol. 2003;134:532–537
  17. Hafler DA, Slavik JM, Anderson DE, O'Connor KC, De Jager P, Baecher-Allan C. Multiple sclerosis. Immunol. Rev. 2005;204:208–231
  18. Hazenberg MD, Otto SA, Cohen Stuart JW, Verschuren MC, Borleffs JC, Boucher CA, et al. Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection. Nat. Med. 2000;6:1036–1042
  19. Hug A, Korporal M, Schroder I, Haas J, Glatz K, Storch-Hagenlocher B, et al. Thymic export function and T cell homeostasis in patients with relapsing remitting multiple sclerosis. J. Immunol. 2003;171:432–437
  20. Jameson SC. Maintaining the norm: T-cell homeostasis. Nat. Rev. Immunol. 2002;2:547–556
  21. Jiang Q, Li WQ, Aiello FB, Mazzucchelli R, Asefa B, Khaled AR, et al. Cell biology of IL-7, a key lymphotrophin. Cytokine Growth Factor Rev. 2005;16:513–533
  22. Kilpatrick RD, Rickabaugh T, Hultin LE, Hultin P, Hausner MA, Detels R, et al. Homeostasis of the naive CD4+ T cell compartment during aging. J. Immunol. 2008;180:1499–1507
  23. Kimmig S, Przybylski GK, Schmidt CA, Laurisch K, Mowes B, Radbruch A, et al. Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J. Exp. Med. 2002;195:789–794
  24. King C, Ilic A, Koelsch K, Sarvetnick N. Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell. 2004;117:265–277
  25. Kohler S, Thiel A. Life after the thymus: CD31+ and CD31− human naive CD4+ T-cell subsets. Blood. 2009;113:769–774
  26. Kohler S, Wagner U, Pierer M, Kimmig S, Oppmann B, Mowes B, et al. Post-thymic in vivo proliferation of naive CD4+ T cells constrains the TCR repertoire in healthy human adults. Eur. J. Immunol. 2005;35:1987–1994
  27. Lundmark F, Duvefelt K, Iacobaeus E, Kockum I, Wallstrom E, Khademi M, et al. Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. Nat. Genet. 2007;39:1108–1113
  28. Marrack P, Kappler J. Control of T cell viability. Annu. Rev. Immunol. 2004;22:765–787
  29. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann. Neurol. 2001;50:121–127
  30. Messele T, Abdulkadir M, Fontanet AL, Petros B, Hamann D, Koot M, et al. Reduced naive and increased activated CD4 and CD8 cells in healthy adult Ethiopians compared with their Dutch counterparts. Clin. Exp. Immunol. 1999;115:443–450
  31. Monti P, Scirpoli M, Maffi P, Ghidoli N, De Taddeo F, Bertuzzi F, et al. Islet transplantation in patients with autoimmune diabetes induces homeostatic cytokines that expand autoreactive memory T cells. J. Clin. Invest. 2008;118:1806–1814
  32. Muraro PA, Pette M, Bielekova B, McFarland HF, Martin R. Human autoreactive CD4+ T cells from naive CD45RA+ and memory CD45RO+ subsets differ with respect to epitope specificity and functional antigen avidity. J. Immunol. 2000;164:5474–5481
  33. Poznansky MC, Olszak IT, Evans RH, Wang Z, Foxall RB, Olson DP, et al. Thymocyte emigration is mediated by active movement away from stroma-derived factors. J. Clin. Invest. 2002;109:1101–1110
  34. Prelog M. Aging of the immune system: a risk factor for autoimmunity?. Autoimmun. Rev. 2006;5:136–139
  35. Puissant-Lubrano B, Viala F, Winterton P, Abbal M, Clanet M, Blancher A. Thymic output and peripheral T lymphocyte subsets in relapsing–remitting multiple sclerosis patients treated or not by IFN-beta. J. Neuroimmunol. 2008;193:188–194
  36. Ramagopalan SV, Maugeri NJ, Handunnetthi L, Lincoln MR, Orton SM, Dyment DA, et al. Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1*1501 is regulated by vitamin D. PLoS Genet. 2009;5:e1000369
  37. Sospedra M, Martin R. Immunology of multiple sclerosis. Annu. Rev. Immunol. 2005;23:683–747
  38. Thewissen M, Linsen L, Somers V, Geusens P, Raus J, Stinissen P. Premature immunosenescence in rheumatoid arthritis and multiple sclerosis patients. Ann. N. Y. Acad. Sci. 2005;1051:255–262
  39. Thewissen M, Somers V, Venken K, Linsen L, van Paassen P, Geusens P, et al. Analyses of immunosenescent markers in patients with autoimmune disease. Clin. Immunol. 2007;123:209–218
  40. van den Dool C, de Boer RJ. The effects of age, thymectomy, and HIV Infection on alpha and beta TCR excision circles in naive T cells. J. Immunol. 2006;177:4391–4401

PII: S0165-5728(10)00054-8

doi: 10.1016/j.jneuroim.2010.02.005

Journal of Neuroimmunology
Volume 221, Issue 1 , Pages 73-80 , 15 April 2010

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