Tags

Type your tag names separated by a space and hit enter

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 2008; 205(8):1763-73JE

Abstract

Symptomatic primary Epstein-Barr virus (EBV) infection and elevated humoral immune responses to EBV are associated with an increased risk of developing multiple sclerosis (MS). We explored mechanisms leading to this change in EBV-specific immunity in untreated patients with MS and healthy virus carriers matched for MS-associated HLA alleles. MS patients showed selective increase of T cell responses to the EBV nuclear antigen 1 (EBNA1), the most consistently recognized EBV-derived CD4(+) T cell antigen in healthy virus carriers, but not to other EBV-encoded proteins. In contrast, 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(+) T helper 1 (Th1) precursors and Th1 (but not Th17) polarized effector memory cells. In addition, EBNA1-specific T cells recognized myelin antigens more frequently than other autoantigens that are not associated with MS. Myelin cross-reactive T cells produced IFN-gamma, but differed from EBNA1-monospecific cells in their capability to produce interleukin-2, indicative of a polyfunctional phenotype as found in controlled chronic viral infections. Our data support the concept that clonally expanded EBNA1-specific CD4(+) T cells potentially contribute to the development of MS by cross-recognition of myelin antigens.

Authors+Show Affiliations

Laboratory of Viral Immunobiology, Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10065, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18663124

Citation

Lünemann, Jan D., et al. "EBNA1-specific T Cells From Patients With Multiple Sclerosis Cross React With Myelin Antigens and Co-produce IFN-gamma and IL-2." The Journal of Experimental Medicine, vol. 205, no. 8, 2008, pp. 1763-73.
Lünemann JD, Jelcić I, Roberts S, et al. 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. 2008;205(8):1763-73.
Lünemann, J. D., Jelcić, I., Roberts, S., Lutterotti, A., Tackenberg, B., Martin, R., & Münz, C. (2008). EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-gamma and IL-2. The Journal of Experimental Medicine, 205(8), pp. 1763-73. doi:10.1084/jem.20072397.
Lünemann JD, et al. 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. 2008 Aug 4;205(8):1763-73. PubMed PMID: 18663124.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-gamma and IL-2. AU - Lünemann,Jan D, AU - Jelcić,Ilijas, AU - Roberts,Susanne, AU - Lutterotti,Andreas, AU - Tackenberg,Björn, AU - Martin,Roland, AU - Münz,Christian, Y1 - 2008/07/28/ PY - 2008/7/30/pubmed PY - 2008/8/20/medline PY - 2008/7/30/entrez SP - 1763 EP - 73 JF - The Journal of experimental medicine JO - J. Exp. Med. VL - 205 IS - 8 N2 - Symptomatic primary Epstein-Barr virus (EBV) infection and elevated humoral immune responses to EBV are associated with an increased risk of developing multiple sclerosis (MS). We explored mechanisms leading to this change in EBV-specific immunity in untreated patients with MS and healthy virus carriers matched for MS-associated HLA alleles. MS patients showed selective increase of T cell responses to the EBV nuclear antigen 1 (EBNA1), the most consistently recognized EBV-derived CD4(+) T cell antigen in healthy virus carriers, but not to other EBV-encoded proteins. In contrast, 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(+) T helper 1 (Th1) precursors and Th1 (but not Th17) polarized effector memory cells. In addition, EBNA1-specific T cells recognized myelin antigens more frequently than other autoantigens that are not associated with MS. Myelin cross-reactive T cells produced IFN-gamma, but differed from EBNA1-monospecific cells in their capability to produce interleukin-2, indicative of a polyfunctional phenotype as found in controlled chronic viral infections. Our data support the concept that clonally expanded EBNA1-specific CD4(+) T cells potentially contribute to the development of MS by cross-recognition of myelin antigens. SN - 1540-9538 UR - https://www.unboundmedicine.com/medline/citation/18663124/EBNA1_specific_T_cells_from_patients_with_multiple_sclerosis_cross_react_with_myelin_antigens_and_co_produce_IFN_gamma_and_IL_2_ L2 - http://jem.rupress.org/cgi/pmidlookup?view=long&pmid=18663124 DB - PRIME DP - Unbound Medicine ER -