Department of Immunology, Westmead Millennium Institute, University of Sydney,
Darcy Road, Westmead 2145, Australia.
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.
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