Cutting edge: the Th1 response inhibits the generation of peripheral regulatory T cells.
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.
Caretto
David
D
Department of Pathology, University of California, San Francisco, San Francisco, CA 94143-0511, USA.
Katzman
Shoshana D
SD
Villarino
Alejandro V
AV
Gallo
Eugenio
E
Abbas
Abul K
AK
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma