In their study, Mercer et al. (1) show that IL-17–producing T cells differentiate from CCR6+ naive CD4 T cells from adult peripheral blood, both conventional and T regulatory cells (nTregs). These results are in line with our recent data showing that TH17 cells can differentiate from nTregs in adult circulating lymphocytes (2). The authors also obtained differentiation of TH17 cells from total CD4+CCR6+ T cells from umbilical cord blood (UBC), although significantly less efficiently. Because of the low proportions of CCR6+ cells in UBC, however, they could not assess CCR6+ conventional CD4 T cells and Tregs separately. As mentioned by the authors, IL-17–secreting cells are found among Helios Tregs that likely correspond to peripherally-induced Tregs rather than thymically-derived Tregs. As was recently reported, nTregs in adults include Helios+ and Helios cells, the latter representing ∼30% of total nTregs (3). We showed, however, that Helios Tregs are undetectable in UBC, in which nTregs are, in contrast, abundant (4). To directly assess the presence of TH17 precursors in nTregs from UBC, we isolated them by cell sorting and differentiated them in the presence of TH17 polarizing factors. However, we failed to obtain a significant differentiation of IL-17–secreting cells from UBC nTregs. Thus, whereas differentiation of TH17 cells can indeed occur from phenotypically naive Tregs of adults, most FOXP3+Helios Treg precursors of TH17 cells appear to develop in the periphery after birth, and may therefore be, despite their naive phenotype, peripherally-induced Tregs rather than thymically-derived Tregs.

Abbreviations used in this article:

nTreg

naive T regulatory cell

Treg

T regulatory cell

UBC

umbilical cord blood

1
Mercer
F.
,
Khaitan
A.
,
Kozhaya
L.
,
Aberg
J. A.
,
Unutmaz
D.
.
2014
.
Differentiation of IL-17–producing effector and regulatory human T cells from lineage-committed naive precursors
.
J. Immunol.
193
:
1047
1054
.
2
Valmori
D.
,
Raffin
C.
,
Raimbaud
I.
,
Ayyoub
M.
.
2010
.
Human RORγt+ TH17 cells preferentially differentiate from naive FOXP3+Treg in the presence of lineage-specific polarizing factors
.
Proc. Natl. Acad. Sci. USA
107
:
19402
19407
.
3
Himmel
M. E.
,
MacDonald
K. G.
,
Garcia
R. V.
,
Steiner
T. S.
,
Levings
M. K.
.
2013
.
Helios+ and Helios cells coexist within the natural FOXP3+ T regulatory cell subset in humans
.
J. Immunol.
190
:
2001
2008
.
4
Ayyoub
M.
,
Raffin
C.
,
Valmori
D.
.
2013
.
Comment on “Helios+ and Helios cells coexist within the natural FOXP3+ T regulatory cell subset in humans
.”
J. Immunol.
190
:
4439
4440
.