Phenotypic analysis of T regulatory cells in multiple sclerosis patients — ASN Events
  1. Schedule
  2. Poster Session One & Burnet Oration Cocktail Function
  3. Phenotypic analysis of T regulatory cells in multiple sclerosis patients

Phenotypic analysis of T regulatory cells in multiple sclerosis patients (#187)

Andrew D. Lam 1 , Christopher H.Y. CHIU 1 , Nirupama D. Verma 1 , Catherine M. Robinson 1 , Giang T. Tran 1 , Bruce M. Hall 1 , Suzanne J. Hodgkinson 1
  1. Immune Tolerance Laboratory, Ingham Research Institute, South Western Sydney Clinical School, UNSW, Liverpool, NSW, Australia

Multiple sclerosis (MS) is an autoimmune condition, characterised by chronic demyelinating central nervous system injury. T-regulatory cells (Treg) are key mediators of immunoregulation. Th-like Treg have been identified which phenotypically mirror pro-inflammatory Th1, Th2 and Th17 subsets. Based on our rat studies showing 100-1000 times higher suppressive ability of Th1-like Treg have compared to naïve-thymic-derived Treg, activated Treg may control inflammation in MS. Most studies on MS showed no changes in overall number of Treg. Changes in subpopulations of Treg, especially related to CD45RA expression have been reported.

 

Here we examined expression of CD45RA on CD4+CD25+CD127lo FOXP3 Treg, to identify activated Treg that had high expression FOXP3 and CD25 consistent with activated and possibly antigen specific Treg. We also examine expression of chemokine receptor specific to Th1-like Treg (CXCR3), Th2-like Treg (CCR8), Th17-like Treg (CCR6) and naïve tTreg (CCR7).   Analysis of CD45RA and FoxP3 expression within CD4+T cells and Treg identified three populations: CD45RA+FOXP3+, CD45RA-FOXP3+ and a third CD45RA-Foxp3hi population that includes activated Treg.  Samples were also assessed for changes in chemokine receptor expression (CXCR3, CCR6 and CCR7) within Treg population subsets in MS patients compared to healthy controls.

 

Unexpectedly, we observed an increase in the proportion of CD45RA-Foxp3hi Treg population to 20.7% in MS patients (n=19) compared to 5.8% in healthy controls (p<0.01). A limited number of treatment-naïve MS patients had an increase to 15% that was greater than controls.

 

Flow cytometry analysis of PBMC showed a marked increase in the frequencies of Treg subtypes based on CD45RA and FOXP3 expression suggesting altered Treg phenotype in MS patients. Changes in chemokine receptor expressing Treg phenotypes, if any, may provide further information on Th-like Treg phenotypes in MS.  We are also examining the effects of disease modifying therapy on these subpopulations in MS patients.

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