CD6: New low/negative surface marker for human FOXP3+ naturally-occurring regulatory T-cells
Natural T-regulatory cells, nTreg, are responsible for the maintenance of dominant self tolerance.
nTreg cells play an important role in the prevention of autoimmune disorders, allergy,
and in maintenance of fetal maternal tolerance and organ graft tolerance. For these reasons
nTreg cells have been the subject of extensive research in the past decade. While the
nuclear transcription factor, FOXP3, uniquely defines nTreg cells, there is a need for more
convenient surface markers that can be used for nTreg isolation. Several surface markers
have been already identified. Among them, CD25 and CD127 are the most commonly
used. We report here the identification of CD6 as a low/negative surface marker for natural
occurring regulatory T-cell (nTreg). CD6 is an important costimulatory molecule in T cell
response. Lack of CD6 expression on nTreg may have significant biological consequences
as it could explain anergy and peripheral antigen-induced tolerance, a central characteristic
of nTreg suppressor cells. The high level of FOXP3+ cells afforded by CD4+CD25+CD6lo/-CD-
127lo/- marker combination provides a new approach for identification, enrichment and isolation
of nTreg by surface staining. In addition, CD4+CD25+CD6lo/-CD127lo/- nTreg functional
differentiation stages can be assessed based on the expression of CD45RA and CCR4
markers, where CD45RA-CCR4hiHLA-DR+ cells could represent a mature effector stage of
the nTreg population. This allows analysis of nTreg differentiation using only surface markers.
Lack of or low CD6 expression on nTreg could contribute to a better understanding of
the biology of nTreg immune regulation.