CD127 immunophenotyping suggests altered CD4+ T cell regulation in primary progressive multiple sclerosis

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+CD25Hi (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+CD25Hi (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+CD25Hi 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.