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 fork-head 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.
ASJC Scopus subject areas
- Immunology and Allergy