title: HLA-E restricted CD8+ T cell subsets are phenotypically altered in multiple sclerosis patients.
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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our study indicates that the HLA-E system is altered in MS and could play a regulatory role in disease.
authors.affiliation: Biomedical Research Institute, Hasselt University, Belgium.
authors.forename: Kim
authors.initials: K
authors.lastname: Pannemans
authors.affiliation: Biomedical Research Institute, Hasselt University, Belgium.
authors.forename: Bieke
authors.initials: B
authors.lastname: Broux
authors.affiliation: Laboratory for Neuroimmunology, KULeuven, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Goris
authors.affiliation: Laboratory for Neuroimmunology, KULeuven, Belgium.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Dubois
authors.affiliation: Biomedical Research Institute, Hasselt University, Belgium Department of Health Care, PHL University College, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Broekmans
authors.affiliation: Biomedical Research Institute, Hasselt University, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Van Wijmeersch
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Geraghty
authors.affiliation: Biomedical Research Institute, Hasselt University, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Stinissen
authors.affiliation: Biomedical Research Institute, Hasselt University, Belgium niels.hellings@uhasselt.be.
authors.forename: Niels
authors.initials: N
authors.lastname: Hellings
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult; D000097625:HLA-E Antigens
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; D015395:Histocompatibility Antigens Class I; D018836:Inflammation Mediators; D055654:NK Cell Lectin-Like Receptor Subfamily C; D000097625:HLA-E Antigens; C418974:FOXP3 protein, human; C527059:KLRC2 protein, human
keywords: CD8+ T cells; HLA-E; Multiple sclerosis; autoreactive T cells; cytotoxic T cells; polymorphisms; regulatory T cells