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Unstable regulatory T cells, enriched for naïve and Nrp1 neg cells, are purged after fate challenge
Ist Teil von
Science immunology, 2021-07, Vol.6 (61)
Ort / Verlag
United States
Erscheinungsjahr
2021
Quelle
MEDLINE
Beschreibungen/Notizen
Regulatory T cells (T
) are indispensable for the control of immune homeostasis and have clinical potential as a cell therapy for treating autoimmunity. T
can lose expression of the lineage-defining Foxp3 transcription factor and acquire effector T cell (T
) characteristics, a process referred to as T
plasticity. The extent and reversibility of such plasticity during immune responses remain unknown. Here, using a murine genetic fate-mapping system, we show that T
stability is maintained even during exposure to a complex microbial/antigenic environment. Furthermore, we demonstrate that the observed plasticity of T
after adoptive transfer into a lymphopenic environment is a property limited to only a subset of the T
population, with the nonconverting majority of T
being resistant to plasticity upon secondary stability challenge. The unstable T
fraction is a complex mixture of phenotypically distinct T
, enriched for naïve and neuropilin-1-negative T
, and includes peripherally induced T
and recent thymic emigrant T
These results suggest that a "purging" process can be used to purify stable T
that are capable of robust fate retention, with potential implications for improving cell transfer therapy.