Cutting edge: the Th1 response inhibits the generation of peripheral regulatory T cells

D Caretto, SD Katzman, AV Villarino… - The journal of …, 2010 - journals.aai.org
D Caretto, SD Katzman, AV Villarino, E Gallo, AK Abbas
The journal of immunology, 2010journals.aai.org
The possibility that effector T cells can be converted into forkhead box P3+ regulatory T cells
(Tregs) has potential therapeutic implications. To analyze the relationship between Th1
effectors and Tregs, we have used a model of systemic autoimmunity in which both effector
and Tregs arise from a single population specific for a transgene-encoded systemic protein.
In vitro, the presence of IFN-γ inhibits Treg generation during activation. Using IFN-γ reporter
mice, we demonstrate that IFN-γ–producing cells tend not to develop into Tregs, and Th1 …
Abstract
The possibility that effector T cells can be converted into forkhead box P3+ regulatory T cells (Tregs) has potential therapeutic implications. To analyze the relationship between Th1 effectors and Tregs, we have used a model of systemic autoimmunity in which both effector and Tregs arise from a single population specific for a transgene-encoded systemic protein. In vitro, the presence of IFN-γ inhibits Treg generation during activation. Using IFN-γ reporter mice, we demonstrate that IFN-γ–producing cells tend not to develop into Tregs, and Th1 priming of T cells prior to cell transfer limits the number of forkhead box P3+ T cells generated in vivo. Moreover, transfer of IFN-γ−/− or STAT1−/− T cells resulted in an increase in the number of Tregs. These data support a role for Th1 effector molecules and transcription factors in the control of peripheral Treg generation and demonstrates the limited plasticity of Th1 populations.
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