title: CD127 immunophenotyping suggests altered CD4+ T cell regulation in primary progressive multiple sclerosis.
abstract: Aberrant regulatory T cell populations, characterised by a wide array of CD markers, have been identified in many autoimmune diseases. CD127 has recently been identified as a specific marker for the CD4(+)CD25(Hi) (Tregs) subset. CD127 is the first non-HLA gene to have its association with multiple sclerosis widely replicated. We demonstrate that the regulatory or suppressor T cells CD4(+)CD25(Hi) (Tregs), CD8(+)CD28(-), and CD3(+)CD56(+) (NKT) all produce low levels of CD127, and so could be at a disadvantage in survival and/or proliferation where IL7 is limiting. The remissions seen in relapsing remitting multiple sclerosis (RRMS) could be driven by regulatory T cells, and the absence of remissions seen in primary progressive MS (PPMS) may point to a particularly reduced function of this cell subset. We found that the proportions of CD4(+)FoxP3(+)CD25(Hi) regulatory T cells were not aberrant in PPMS. There was, however, a trend towards reduced FoxP3 expression per cell in this fraction (p<0.083), which has been highly correlated with suppressor function. Notably, we found that the target of regulatory T cells, the CD4(+)CD25(-) cells, was in excess (p<0.009); and in PPMS a protective CD127 haplotype is correlated with higher CD127 expression (p<0.01). These data support further investigations into the regulatory T cell immunophenotype in MS.
authors.affiliation: Department of Immunology, Westmead Millennium Institute, University of Sydney, Darcy Road, Westmead 2145, Australia.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: McKay
authors.forename: Louisa I
authors.initials: LI
authors.lastname: Swain
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Schibeci
authors.forename: Justin P
authors.initials: JP
authors.lastname: Rubio
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Kilpatrick
authors.forename: Robert N
authors.initials: RN
authors.lastname: Heard
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Stewart
authors.forename: David R
authors.initials: DR
authors.lastname: Booth
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000276:immunology; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology* / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000954:Antigens, Surface; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053699:Interleukin-7 Receptor alpha Subunit