EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-γ and IL-2
| Autor: | Ilijas Jelčić, Susanne Roberts, Jan D. Lünemann, Christian Münz, Björn Tackenberg, Andreas Lutterotti, Roland Martin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Epstein-Barr Virus Infections Herpesvirus 4 Human Multiple Sclerosis T cell Immunology Human leukocyte antigen Biology Cross Reactions Antibodies Viral Autoantigens 03 medical and health sciences Myelin Interferon-gamma 0302 clinical medicine Immune system Antigen T-Lymphocyte Subsets hemic and lymphatic diseases medicine Immunology and Allergy Cytotoxic T cell Humans Pan-T antigens 030304 developmental biology Aged 0303 health sciences Multiple sclerosis Brief Definitive Report Myelin Basic Protein Middle Aged medicine.disease Virology 3. Good health medicine.anatomical_structure Epstein-Barr Virus Nuclear Antigens Case-Control Studies Immunoglobulin G Brief Definitive Reports Interleukin-2 Female 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | 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-γ, 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. |
| Databáze: | OpenAIRE |
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