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Increased HLA ‐E expression in white matter lesions in multiple sclerosis
Author(s) -
Durrenberger Pascal F.,
Webb Louise V.,
Sim Malcolm J. W.,
Nicholas Richard S.,
Altmann Daniel M.,
Boyton Rosemary J.
Publication year - 2012
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12012
Subject(s) - multiple sclerosis , pathogenesis , biology , white matter , central nervous system , immunology , immune system , inflammation , human leukocyte antigen , pathology , medicine , antigen , neuroscience , magnetic resonance imaging , radiology
Summary The molecular mechanisms underpinning central nervous system damage in multiple sclerosis ( MS ) are complex and it is widely accepted that there is an autoimmune component. Both adaptive and innate immune effector mechanisms are believed to contribute to tissue disease aetiology. HLA ‐E is a non‐classical MHC class Ib molecule that acts as the ligand for the NKG 2 A inhibitory receptor present on natural killer ( NK ) and CD 8 + cells. Peptide binding and stabilization of HLA ‐ E is often considered to signal infection or cell stress. Here we examine the up‐regulation of HLA ‐ E in MS brain tissue. Expression is significantly increased in white matter lesions in the brain of MS patients compared with white matter of neurologically healthy controls. Furthermore, using quantitative immunohistochemistry and confocal microscopy, we show increased HLA ‐ E protein expression in endothelial cells of active MS lesions. Non‐inflammatory chronic lesions express significantly less HLA ‐ E protein, comparable to levels found in white matter from controls. Increased HLA ‐ E protein levels were associated with higher scores of inflammation. These results suggest the potential for an effect in central nervous system pathogenesis from HLA ‐ E modulation in stressed tissue. Co‐localization with infiltrating CD 8 + cells implicates a possible role for HLA ‐ E ‐restricted regulatory CD 8 + cells, as has been proposed in other autoimmune diseases.