TY - JOUR
T1 - IL-17-and IFN-γ-secreting Foxp3+ T cells infiltrate the target tissue in experimental autoimmunity
AU - Esposito, Marianna
AU - Ruffini, Francesca
AU - Bergami, Alessandra
AU - Garzetti, Livia
AU - Borsellino, Giovanna
AU - Battistini, Luca
AU - Martino, Gianvito
AU - Furlan, Roberto
PY - 2010/12/15
Y1 - 2010/12/15
N2 - CD4+Foxp3+ regulatory T cells (Tregs) have been considered crucial in controlling immune system homeostasis, and their derangement is often associated to autoimmunity. Tregs identification is, however, difficult because most markers, including CD25 and Foxp3, are shared by recently activated T cells. We show in this paper that CD4+Foxp3+ T cells are generated in peripheral lymphoid organs on immunization and readily accumulate in the target organ of an autoimmune reaction, together with classical inflammatory cells, constituting up to 50% of infiltrating CD4+ T cells. Most CD4+Foxp3+ T cells are, however, CD252 and express proinflammatory cytokines such as IL-17 and IFN-g, questioning their suppressive nature. Moreover, in vitro CD4+ T lymphocytes from naive and autoimmune mice, stimulated to differentiate into Th1, Th2, Th17, and induced Tregs, display early mixed expression of lineage-specific markers. These results clearly point to an unprecedented plasticity of naive CD4+ T cells, that integrating inflammatory signals may change their fate from the initial lineage commitment to a different functional phenotype.
AB - CD4+Foxp3+ regulatory T cells (Tregs) have been considered crucial in controlling immune system homeostasis, and their derangement is often associated to autoimmunity. Tregs identification is, however, difficult because most markers, including CD25 and Foxp3, are shared by recently activated T cells. We show in this paper that CD4+Foxp3+ T cells are generated in peripheral lymphoid organs on immunization and readily accumulate in the target organ of an autoimmune reaction, together with classical inflammatory cells, constituting up to 50% of infiltrating CD4+ T cells. Most CD4+Foxp3+ T cells are, however, CD252 and express proinflammatory cytokines such as IL-17 and IFN-g, questioning their suppressive nature. Moreover, in vitro CD4+ T lymphocytes from naive and autoimmune mice, stimulated to differentiate into Th1, Th2, Th17, and induced Tregs, display early mixed expression of lineage-specific markers. These results clearly point to an unprecedented plasticity of naive CD4+ T cells, that integrating inflammatory signals may change their fate from the initial lineage commitment to a different functional phenotype.
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U2 - 10.4049/jimmunol.1001519
DO - 10.4049/jimmunol.1001519
M3 - Article
C2 - 21098230
AN - SCOPUS:78650655423
VL - 185
SP - 7467
EP - 7473
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -