title: Increased expression of Tbet in CD4(+) T cells from clinically isolated syndrome patients at high risk of conversion to clinically definite MS.
abstract: BACKGROUND
  The ability to identify clinically isolated syndrome (CIS) patients at high risk of progression to clinically definite multiple sclerosis (CDMS) would be clinically beneficial. The initiation of T cell mediated autoimmune diseases such as multiple sclerosis (MS) requires the initial inappropriate activation and differentiation of auto-reactive CD4(+) T cells. The quiescence of naive T cells is actively maintained by molecules such as TOB1, which control the threshold of activation. Upon activation, CD4(+) T cells can differentiate into various subsets depending on the milieu present. Th1 and Th17 cells are strongly implicated in MS, while regulatory T (Treg) cells constrain autoimmune inflammation and prevent autoimmunity.
  
  
  RESULTS
  We therefore investigated the expression of TOB1, CD44 and Treg, Th1 and Th17 transcription factors in relation to CIS progression. The expression of TOB1, CD44, FOXP3, TBX21 and RORC genes were measured in CD4(+) T cells from 10 healthy controls, 20 CIS patients within 3 months of initial clinical presentation and 10 relapsing remitting MS patients sampled within 2 months of relapse. CIS patients were subsequently grouped into those who converted to CDMS within 1 year and those who remained CIS. No differences in the expression of TOB1, CD44, FOXP3 and RORC were observed. There was a significant increase in the expression of the Th1 transcription factor Tbet, encoded by TBX21, in CIS patients that converted within 1 year compared with those who did not.
  
  
  CONCLUSIONS
  This pilot data suggests a role for Th1 cells in CIS progression and warrants further evaluation in a larger cohort.
authors.affiliation: Schools of Biochemistry and Immunology and Medicine, Trinity Biomedical Science Institute, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland.
authors.forename: Sharee A
authors.initials: SA
authors.lastname: Basdeo
authors.affiliation: Department of Neurology, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.|School of Medicine and Medical Science, University College Dublin, Dublin 2, Ireland.
authors.forename: Siobhan
authors.initials: S
authors.lastname: Kelly
authors.affiliation: Department of Neurology, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.|School of Medicine and Medical Science, University College Dublin, Dublin 2, Ireland.
authors.forename: Karen
authors.initials: K
authors.lastname: O'Connell
authors.affiliation: Department of Neurology, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.|School of Medicine and Medical Science, University College Dublin, Dublin 2, Ireland.
authors.forename: Niall
authors.initials: N
authors.lastname: Tubridy
authors.affiliation: Department of Neurology, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.|School of Medicine and Medical Science, University College Dublin, Dublin 2, Ireland.
authors.forename: Christopher
authors.initials: C
authors.lastname: McGuigan
authors.affiliation: Schools of Biochemistry and Immunology and Medicine, Trinity Biomedical Science Institute, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Fletcher
keywords: Clinically isolated syndrome; Multiple sclerosis; T cells; TOB1; Tbet