title: CRYAB modulates the activation of CD4+ T cells from relapsing-remitting multiple sclerosis patients.
abstract: BACKGROUND
  Suppression of activation of pathogenic CD4(+) T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS.
  
  
  OBJECTIVE
  We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease.
  
  
  METHODS
  CD4(+) T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73-92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated.
  
  
  RESULTS
  The secretion of pro-inflammatory cytokines by CD4(+) T cells was decreased in the presence of CRYAB in a subset of relapsing-remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8(+) T cells, in CD4(+) T cells of MS patients that displayed suppressed cytokine production (responders).
  
  
  CONCLUSIONS
  CRYAB may be capable of suppressing the activation of CD4(+) T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.
authors.affiliation: Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.
authors.forename: Que Lan
authors.initials: QL
authors.lastname: Quach
authors.forename: Luanne M
authors.initials: LM
authors.lastname: Metz
authors.forename: Jenna C
authors.initials: JC
authors.lastname: Thomas
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Rothbard
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
authors.forename: Shalina S
authors.initials: SS
authors.lastname: Ousman
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult; D038203:alpha-Crystallin B Chain / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D010446:Peptide Fragments; D038203:alpha-Crystallin B Chain
keywords: CD4+ T cells; CRYAB; Multiple sclerosis; alphaB-crystallin; microRNA