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PLZF(+) Innate T Cells Support the TGF-?-Dependent Generation of
Activated/Memory-Like Regulatory T Cells
#MMPMID27101876
Kang BH
; Park HJ
; Park HJ
; Lee JI
; Park SH
; Jung KC
Mol Cells
2016[Jun]; 39
(6
): 468-76
PMID27101876
show ga
PLZF-expressing invariant natural killer T cells and CD4 T cells are unique
subsets of innate T cells. Both are selected via thymocyte-thymocyte interaction,
and they contribute to the generation of activated/memory-like CD4 and CD8 T
cells in the thymus via the production of IL-4. Here, we investigated whether
PLZF(+) innate T cells also affect the development and function of Foxp3(+)
regulatory CD4 T cells. Flow cytometry analysis of the thymus and spleen from
both CIITA transgenic C57BL/6 and wild-type BALB/c mice, which have abundant
PLZF(+) CD4 T cells and invariant natural killer T cells, respectively, revealed
that Foxp3(+) T cells in these mice exhibited a CD103(+) activated/memory-like
phenotype. The frequency of CD103(+) regulatory T cells was considerably
decreased in PLZF(+) cell-deficient CIITA(Tg)Plzf(lu/lu) and BALB/c.CD1d(-/-)
mice as well as in an IL-4-deficient background, such as in CIITA(Tg)IL-4(-/-)
and BALB/c.lL-4(-/-) mice, indicating that the acquisition of an
activated/memory-like phenotype was dependent on PLZF(+) innate T cells and IL-4.
Using fetal thymic organ culture, we further demonstrated that IL-4 in concert
with TGF-? enhanced the acquisition of the activated/memory-like phenotype of
regulatory T cells. In functional aspects, the activated/memory-like phenotype of
Treg cells was directly related to their suppressive function; regulatory T cells
of CIITA(Tg)PIV(-/-) mice more efficiently suppressed ovalbumin-induced allergic
airway inflammation compared with their counterparts from wild-type mice. All of
these findings suggest that PLZF(+) innate T cells also augmented the generation
of activated/memory-like regulation via IL-4 production.
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