title: Analysis of CD4+ CD8+ double-positive T cells in blood, cerebrospinal fluid and multiple sclerosis lesions.
abstract: T cells with a CD4(+) CD8(+) double-positive (DP) phenotype are present in small numbers in the peripheral blood of healthy humans and may have anti-viral capacities. Here we investigate numbers and function of DP T cells in patients with relapsing-remitting multiple sclerosis (MS), either treatment-naive or under therapy with natalizumab. Flow cytometry analysis revealed that frequencies of circulating DP T cells in treatment-naive and natalizumab-treated MS patients are comparable to healthy controls. These cells have a memory phenotype with cytotoxic potential, express high levels of CD49d and are similarly functional in treatment-naive as well as natalizumab-treated MS patients. DP T cells were enriched in the cerebrospinal fluid, but do not invade acutely inflamed MS lesions. In conclusion, DP T cells are functional in MS and may play a role in the immune surveillance of the central nervous system, but do not display functional impairment under natalizumab therapy.
authors.affiliation: Department of Neurology, Friedrich-Alexander University of Erlangen, Erlangen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Waschbisch
authors.forename: L
authors.initials: L
authors.lastname: Sammet
authors.forename: S
authors.initials: S
authors.lastname: Schröder
authors.forename: D-H
authors.initials: DH
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Barrantes-Freer
authors.forename: C
authors.initials: C
authors.lastname: Stadelmann
authors.forename: R A
authors.initials: RA
authors.lastname: Linker
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D000956:Antigens, Viral / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D016022:Case-Control Studies; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007577:JC Virus / Q000276:immunology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D000069442:Natalizumab; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000956:Antigens, Viral; D015704:CD4 Antigens; D016827:CD8 Antigens; D000069442:Natalizumab
keywords: JC virus; cerebrospinal fluid; memory T cells; natalizumab
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3794-9
references.pmid: 15731353
references.citation: J Immunol. 1994 Feb 15;152(4):1509-14
references.pmid: 8120365
references.citation: J Immunol. 2002 Jun 15;168(12):6173-80
references.pmid: 12055230
references.citation: Blood. 2004 Jul 15;104(2):478-86
references.pmid: 15044252
references.citation: Ann Neurol. 2006 May;59(5):748-54
references.pmid: 16634035
references.citation: J Neuroimmunol. 2012 Aug 15;249(1-2):86-92
references.pmid: 22633193
references.citation: PLoS One. 2011;6(5):e20145
references.pmid: 21647449
references.citation: Scand J Haematol. 1985 Aug;35(2):233-9
references.pmid: 3876598
references.citation: Clin Exp Immunol. 1981 Jul;45(1):1-8
references.pmid: 6458432
references.citation: J Immunol. 2012 May 1;188(9):4289-96
references.pmid: 22461689
references.citation: Eur J Immunol. 1987 Dec;17(12):1815-9
references.pmid: 2961576
references.citation: Ann Neurol. 1983 Mar;13(3):227-31
references.pmid: 6847134
references.citation: Biochem Biophys Res Commun. 1993 Mar 15;191(2):601-9
references.pmid: 8461016
references.citation: Arch Neurol. 2006 Oct;63(10):1383-7
references.pmid: 17030653
references.citation: Cell Immunol. 1993 Jul;149(2):376-89
references.pmid: 8101138
references.citation: Ann Neurol. 2011 Feb;69(2):292-302
references.pmid: 21387374
references.citation: Ann Neurol. 1987 Jul;22(1):89-93
references.pmid: 3498435
references.citation: Ann Neurol. 2013 Jul;74(1):84-90
references.pmid: 23526716
references.citation: J Clin Immunol. 1993 Mar;13(2):113-8
references.pmid: 8100570
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8389-94
references.pmid: 12829791
references.citation: Ann Neurol. 1994 Jan;35(1):65-73
references.pmid: 8285595
references.citation: Ann N Y Acad Sci. 2012 Jul;1262:27-36
references.pmid: 22823432
references.citation: N Engl J Med. 2012 May 17;366(20):1870-80
references.pmid: 22591293
references.citation: J Infect Dis. 1998 Oct;178(4):1158-62
references.pmid: 9806050
references.citation: J Virol. 2013 May;87(10):6055-9
references.pmid: 23514886
references.citation: Clin Exp Immunol. 1993 Sep;93(3):430-6
references.pmid: 8370171
references.citation: Brain Pathol. 2013 Jan;23(1):2-12
references.pmid: 22612622
references.citation: J Immunol. 1985 Apr;134(4):2281-6
references.pmid: 2982943