Cutting Edge: The Th1 Response Inhibits the Generation of Peripheral Regulatory T Cells

• Published in: The Journal of immunology (1950) 2010-01, Vol.184 (1), p.30-34
• Main Authors: Caretto, David, Katzman, Shoshana D, Villarino, Alejandro V, Gallo, Eugenio, Abbas, Abul K
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Cell Differentiation - immunology; Flow Cytometry; Forkhead Transcription Factors; Interferon-gamma - immunology; Lymphocyte Activation - immunology; Mice; Mice, Transgenic; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; Th1 Cells - cytology; Th1 Cells - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0903412

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-gamma inhibits Treg generation during activation. Using IFN-gamma reporter mice, we demonstrate that IFN-gamma-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-gamma(-/-) 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.