In:
Multiple Sclerosis Journal, SAGE Publications, Vol. 20, No. 7 ( 2014-06), p. 790-801
Abstract:
The importance of Qa-1 restricted CD8 + T cells in regulating autoreactive T cell responses has been demonstrated in animal models for autoimmune disorders, including multiple sclerosis (MS). Objective: We hypothesize that their human variant, HLA-E restricted CD8 + T cells, fulfills a similar regulatory role in man and that these cells are of importance in MS. Methods: A large cohort of MS patients and healthy controls was genotyped for the two known HLA-E polymorphisms. Flow cytometry was used to determine HLA-E expression kinetics and to phenotype HLA-E restricted CD8 + T cells. Immunohistochemistry was performed to investigate HLA-E expression in the central nervous system (CNS) of MS patients. Results: HLA-E is upregulated on immune cells upon in vitro activation and this upregulation is polymorphism-dependent for T and B cells. T and B cells in lesions of MS patients show enhanced HLA-E expression. Furthermore, NKG2C + CD8 + T cells of MS patients have a significantly lower Foxp3 expression, while NKG2A + CD8 + T cells of MS patients produce higher levels of pro-inflammatory cytokines compared to those of healthy individuals. Conclusion: Our study indicates that the HLA-E system is altered in MS and could play a regulatory role in disease.
Type of Medium:
Online Resource
ISSN:
1352-4585
,
1477-0970
DOI:
10.1177/1352458513509703
Language:
English
Publisher:
SAGE Publications
Publication Date:
2014
detail.hit.zdb_id:
2008225-3
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