title: A critical role for virus-specific CD8(+) CTLs in protection from Theiler's virus-induced demyelination in disease-susceptible SJL mice.
abstract: Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) is a relevant mouse model of multiple sclerosis. Infection of susceptible SJL/J mice leads to life-long CNS virus persistence and development of a chronic T cell-mediated autoimmune demyelinating disease triggered via epitope spreading to endogenous myelin epitopes. Potent CNS-infiltrating CD8(+) T cell responses to TMEV epitopes have previously been shown to be induced in both disease-susceptible SJL/J and resistant C57BL/6 mice, in which the virus is rapidly cleared. Specific tolerization of SJL CD8(+) T cells specific for the immunodominant TMEV VP3(159)(-)(166) epitope has no effect on viral load or development of clinical TMEV-IDD, but adoptive transfer of activated CD8(+) VP3(159)(-)(166)-specific T cell blasts shortly after TMEV infection to boost the early anti-viral response leads to clearance of CNS virus and protection from subsequent TMEV-IDD. These studies have important implications for vaccine strategies and treatment of chronic infections in humans.
authors.affiliation: Department of Microbiology and Immunology and Interdepartmental Immunobiology Center, Northwestern University Feinberg School of Medicine, 303, E. Chicago Ave., Chicago, IL 60611, USA.
authors.forename: Meghann Teague
authors.initials: MT
authors.lastname: Getts
authors.forename: Maureen H
authors.initials: MH
authors.lastname: Richards
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Miller
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018188:Cardiovirus Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D003711:Demyelinating Diseases / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D017945:Theilovirus / Q000276:immunology*; D019562:Viral Load
chemical_list: D018984:Epitopes, T-Lymphocyte
references.citation: J Neuroimmunol. 1999 Aug 3;98(2):136-46
references.pmid: 10430047
references.citation: Nat Rev Cancer. 2003 Sep;3(9):666-75
references.pmid: 12951585
references.citation: Mol Immunol. 2001 Dec;38(6):467-73
references.pmid: 11741696
references.citation: Virology. 1990 May;176(1):244-54
references.pmid: 2158691
references.citation: Nat Med. 1997 Oct;3(10):1133-6
references.pmid: 9334726
references.citation: Genetics. 1998 Apr;148(4):1941-9
references.pmid: 9560407
references.citation: Eur J Immunol. 1993 Jan;23(1):46-55
references.pmid: 8419186
references.citation: J Leukoc Biol. 2006 Apr;79(4):652-62
references.pmid: 16415165
references.citation: Viral Immunol. 2001;14(3):227-50
references.pmid: 11572634
references.citation: Lab Invest. 1981 Dec;45(6):504-9
references.pmid: 7321523
references.citation: J Immunol. 1995 Jul 15;155(2):947-57
references.pmid: 7608570
references.citation: J Exp Med. 2001 Jan 15;193(2):181-94
references.pmid: 11148222
references.citation: J Immunol. 1985 Sep;135(3):2145-8
references.pmid: 2991380
references.citation: J Clin Invest. 2005 Jun;115(6):1616-26
references.pmid: 15931392
references.citation: Eur J Immunol. 2004 Oct;34(10):2730-9
references.pmid: 15368289
references.citation: J Neurovirol. 2001 Oct;7(5):409-20
references.pmid: 11582513
references.citation: J Virol. 2007 Jun;81(12):6584-93
references.pmid: 17428853
references.citation: Eur J Immunol. 1993 Sep;23(9):2287-93
references.pmid: 8370406
references.citation: Virology. 1995 Jun 1;209(2):437-44
references.pmid: 7778279
references.citation: J Gen Virol. 1992 Jul;73 ( Pt 7):1861-5
references.pmid: 1629706
references.citation: J Neurol. 2005 Nov;252 Suppl 5:v3-9
references.pmid: 16254699
references.citation: J Gen Virol. 1987 Jun;68 ( Pt 6):1659-67
references.pmid: 2953860
references.citation: J Neurosci Res. 1996 Aug 15;45(4):364-74
references.pmid: 8872896
references.citation: J Neuroimmunol. 2000 Apr 3;104(1):79-84
references.pmid: 10683517
references.citation: J Immunol. 1996 May 15;156(10):4050-8
references.pmid: 8621948
references.citation: Science. 1983 Jan 21;219(4582):308-10
references.pmid: 6217550
references.citation: Nat Rev Immunol. 2009 Apr;9(4):246-58
references.pmid: 19319143
references.citation: Int Immunol. 1994 May;6(5):721-30
references.pmid: 8080842
references.citation: J Immunol. 1985 Aug;135(2):1408-14
references.pmid: 3925009
references.citation: Annu Rev Immunol. 2005;23:683-747
references.pmid: 15771584
references.citation: Curr HIV Res. 2003 Apr;1(2):205-16
references.pmid: 15043203
references.citation: J Immunol. 1994 Jan 15;152(2):919-29
references.pmid: 7506740
references.citation: J Neuroimmunol. 2000 Jul 1;106(1-2):43-52
references.pmid: 10814781
references.citation: Clin Exp Immunol. 2009 Jan;155(1):1-15
references.pmid: 19076824
references.citation: J Clin Virol. 2005 Dec;34 Suppl 1:S108-14
references.pmid: 16461209
references.citation: Nat Med. 2005 Mar;11(3):335-9
references.pmid: 15735651
references.citation: Cell. 1998 May 29;93(5):673-6
references.pmid: 9630211
references.citation: Nat Med. 1998 Feb;4(2):187-193
references.pmid: 9461192
references.citation: J Immunol. 1998 Oct 15;161(8):4437-46
references.pmid: 9780223
references.citation: N Engl J Med. 1995 Oct 19;333(16):1038-44
references.pmid: 7675046
references.citation: J Immunol. 2002 Apr 15;168(8):4173-83
references.pmid: 11937578
references.citation: J Immunol. 1993 Jul 1;151(1):266-76
references.pmid: 8326128
references.citation: J Virol. 2002 Jul;76(13):6577-85
references.pmid: 12050370
references.citation: J Exp Med. 1986 Mar 1;163(3):620-31
references.pmid: 3005466
references.citation: Nat Rev Immunol. 2006 Dec;6(12):930-9
references.pmid: 17124514
references.citation: J Neuroimmunol. 2002 Feb;123(1-2):18-29
references.pmid: 11880145
references.citation: Nat Med. 1996 Feb;2(2):216-23
references.pmid: 8574968
references.citation: J Neuroimmunol. 2001 Jun 1;116(2):125-35
references.pmid: 11438167
references.citation: J Virol. 1998 Sep;72(9):7320-9
references.pmid: 9696828
references.citation: J Immunol. 2000 Nov 1;165(9):5304-14
references.pmid: 11046065
references.citation: J Virol. 1993 Jan;67(1):589-92
references.pmid: 8416386
references.citation: Intervirology. 1997;40(2-3):143-52
references.pmid: 9450231