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Foxp3 + CD25 + regulatory T cells specific for a neo-self-antigen develop at the double-positive thymic stage

2006; National Academy of Sciences; Volume: 103; Issue: 22 Linguagem: Inglês

10.1073/pnas.0603086103

1091-6490

Julie Cabarrocas, Cécile Cassan, Fay Magnusson, Eliane Piaggio, Lennart T. Mars, Jens Derbinski, Bruno Kyewski, David‐Alexandre Gross, Benoı̂t L. Salomon, Khashayarsha Khazaie, Abdelhadi Saoudi, Roland Liblau,

Immunotherapy and Immune Responses

Thymus-derived regulatory T cells (Tregs) expressing CD4, CD25, and the transcription factor Foxp3 play major roles in preventing autoimmunity. The Treg population is enriched in T cells expressing high-avidity self-reactive T cell receptors, and thymic epithelial cells expressing self-antigens (Ag) have been implicated in their induction and/or selection. However, the thymic selection events leading to Treg lineage commitment remain unclear. We followed the thymic development of self-Ag-specific Tregs in double-transgenic mice coexpressing a neo-self-Ag, hemagglutinin (HA) under the control of a neural tissue-specific promoter, and a transgenic class II-restricted T cell antigen receptor specific for HA111-119. Our data show that the promiscuous expression of the HA transgene in thymic epithelial cells is involved in the selective induction and/or expansion of HA-specific Foxp3(+) Treg thymic precursors as early as the double-positive stage.