We thank Drs. Moreira-Teixeira and Leite-de-Moraes for their interest in our paper. From their additional data, it was concluded that FOXP3 was induced in ex vivo invariant NKT (iNKT) upon in vitro exposure of iNKT to TGF-β, rapamycin, and particularly the combination of TGF-β and rapamycin (1). Unresolved in their data as presented is the intracellular localization of FOXP3. Clearly, an analysis thereof would have been instrumental when connecting to our recently published paper. Key in our paper was the observation that suppressive iNKT were characterized by nuclear localization of FOXP3 and that this was only observed when iNKT were cultured in the presence of rapamycin. Though we acknowledge, as was already discussed in our manuscript, that the overall plasticity of iNKT might be higher in ex vivo iNKT cells compared with iNKT cell lines, it is important to realize that a suppressive function was not documented by Moreira-Teixeira et al. using iNKT cultured in the presence of TGF-β alone (2). From our studies, it has become clear that regardless of the presence of TGF-β, mTOR inhibition is sufficient to confer iNKT into FOXP3+ iNKT with suppressive functions (as was also discussed in our manuscript and demonstrated in ex vivo iNKT in supplemental figure 3). Finally, we fully agree with the conclusion of Moreira-Teixeira et al. (1) that a better understanding of the factors controlling iNKT cell functions has the potential to have substantial impact on patient care.

Abbreviation used in this article:

iNKT

invariant NKT.

1
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Leite-de-Moraes
M. C.
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2015
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2
Moreira-Teixeira
L.
,
Resende
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Devergne
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,
Herbeuval
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,
Hermine
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Leite-de-Moraes
M. C.
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2012
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Rapamycin combined with TGF-β converts human invariant NKT cells into suppressive Foxp3+ regulatory cells
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