Premium
Selective Deregulation of EBNA1‐Specific T Cells in Multiple Sclerosis
Author(s) -
Lunemann Jan,
Jelcic Ilijas,
Roberts Susanne,
Lutterotti Andreas,
Tackenberg Bjorn,
Martin Roland,
Munz Christian
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.668.4
Subject(s) - multiple sclerosis , immunology , antigen , immune system , biology , myelin , human leukocyte antigen , myelin basic protein , phenotype , t cell , virology , gene , central nervous system , genetics , neuroscience
Symptomatic primary EBV infection and elevated humoral immune responses to EBV are associated with an increased risk to develop Multiple Sclerosis (MS). We explored mechanisms leading to this change in EBV‐specific immunity in patients with MS and healthy virus carriers matched for expression of MS‐associated HLA alleles. MS patients showed a selective increase of T cell responses to the EBV nuclear antigen‐1 (EBNA1), but not to other EBV‐encoded proteins. Influenza and human cytomegalovirus specific immune control was unchanged in MS. The enhanced response to EBNA1 was mediated by an expanded reservoir of EBNA1‐specific central memory CD4+ Th1 precursors and Th1 (but not Th17)‐polarized effector memory cells which displayed a phenotype indicative of frequent antigen recognition. In addition, EBNA1‐specific T cells recognized myelin antigens more frequently than other autoantigens. Myelin cross‐reactive T cells produced IFN‐g, but differed from EBNA1‐monospecific ones in their capability to produce IL‐2 compatible with a polyfunctional T cell phenotype as found in controlled chronic viral infections. Our data support the concept that clonally expanded EBNA1‐specific T cells potentially contribute to the development of MS by cross‐recognition of myelin antigens.