Foxp3+ CD25+ regulatory T cells specific for a neo-self-antigen develop at the double-positive thymic stage.
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.
Cabarrocas
Julie
J
Institut National de la Santé et de la Recherche Médicale U563, Purpan Hospital, 31000 Toulouse, France.
Cassan
Cécile
C
Magnusson
Fay
F
Piaggio
Eliane
E
Mars
Lennart
L
Derbinski
Jens
J
Kyewski
Bruno
B
Gross
David-Alexandre
DA
Salomon
Benoit L
BL
Khazaie
Khashayarsha
K
Saoudi
Abdelhadi
A
Liblau
Roland S
RS
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D015329:Gene Rearrangement, T-Lymphocyte / Q000276:immunology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006388:Hemagglutinins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D006388:Hemagglutinins; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2