Cutting edge: Intrathymic differentiation of adaptive Foxp3+ regulatory T cells upon peripheral proinflammatory immunization

Thymocytes differentiate into CD4(+) Foxp3(+) regulatory T cells (T(R)) upon interaction between their TCR and peptide-MHC II complexes locally expressed in the thymus. Conversion of naive CD4(+) T cells into T(R) can additionally take place in the periphery under noninflammatory conditions of Ag en...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2010-10, Vol.185 (7), p.3829-3833
Main Authors: Zelenay, Santiago, Bergman, Marie-Louise, Paiva, Ricardo Sousa, Lino, Andreia C, Martins, Ana C, Duarte, João H, Moraes-Fontes, Maria F, Bilate, Angelina M, Lafaille, Juan J, Demengeot, Jocelyne
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - immunology
Encephalomyelitis, Autoimmune, Experimental - immunology
Forkhead Transcription Factors - immunology
Forkhead Transcription Factors - metabolism
Immune Tolerance - immunology
Immunization
Inflammation - immunology
Interleukin-6 - immunology
Mice
Mice, Inbred C57BL
Mice, Transgenic
T-Lymphocyte Subsets - cytology
T-Lymphocyte Subsets - immunology
T-Lymphocytes, Regulatory - cytology
T-Lymphocytes, Regulatory - immunology
Thymus Gland - cytology
Thymus Gland - immunology
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Summary:Thymocytes differentiate into CD4(+) Foxp3(+) regulatory T cells (T(R)) upon interaction between their TCR and peptide-MHC II complexes locally expressed in the thymus. Conversion of naive CD4(+) T cells into T(R) can additionally take place in the periphery under noninflammatory conditions of Ag encounter. In this study, making use of TCR transgenic models naturally devoid of Foxp3(+) cells, we report de novo generation of T(R) upon a single footpad injection of Ag mixed with a classic proinflammatory adjuvant. Abrupt T(R) differentiation upon immunization occurred intrathymically and was essential for robust tolerance induction in a mouse model of spontaneous encephalomyelitis. This phenomenon could be attributed to a specific feature of thymocytes, which, in contrast to mature peripheral CD4(+) T cells, were insensitive to the inhibitory effects of IL-6 on the induction of Foxp3 expression. Our findings uncover a pathway for T(R) generation with major implications for immunity and tolerance induction.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1001281