ArrayExpress Uploader0mouse29 days oldanti-CD3 treatmentBDC2.5 TCR tg RAG1o/o Foxp3GFP NOD12 days (after treatment)29 days oldanti-CD3 treatmentBDC2.5 TCR tg RAG1o/o Foxp3GFP NOD12 days (after treatment)28 days oldanti-CD3 treatmentBDC2.5 TCR tg RAG1o/o Foxp3GFP NOD11 days (after treatment)29 days oldno treatmentBDC2.5 TCR tg RAG1+/o Foxp3GFP NODnot specified28 days oldno treatmentBDC2.5 TCR tg RAG1+/o Foxp3GFP NODnot specified28 days oldno treatmentBDC2.5 TCR tg RAG1+/o Foxp3GFP NODnot specified6133arrayexpress_sid6Treatment with anti-CD3 is a promising therapeutic approach for autoimmune diabetes, but its mechanism of action remains unclear. Foxp3+...E-GEOD-22527/profile/8773/arrayexpressuploader46cellil-7rinterleukininterleukin-2lymphspleenthymusDec.12, 2014Falseanti-cd3-therapy-permits-regulatory-t-cells-to-surE-GEOD-22527_A-AFFY-45Anti-CD3 therapy permits regulatory T cells to surmount T cell receptor-specified peripheral niche constraintsNov.11, 2014Treatment with anti-CD3 is a promising therapeutic approach for autoimmune diabetes, but its mechanism of action remains unclear. Foxp3+ regulatory T (Treg) cells may be involved, but the evidence has been conflicting, and there is great uncertainty as to possible mechanistic connections. We investigated this issue in mice derived from the NOD model, which were engineered mice in which Treg populations were perturbed, or could be manipulated by acute ablation or transfer. The data highlighted the involvement of Foxp3+ cells in anti-CD3 action. Rather than a generic influence on all Treg cells, the therapeutic effect seemed to involve an striking expansion of previously constrained Treg cell populations; this expansion occurred not through conversion from Foxp3- Tconv cells but from a dramatic proliferative expansion. We found that Treg cells are normally constrained by TCR-specific niches in secondary lymphoid organs, and that intraclonal competition restrains their possibility for conversion and expansion in the spleen and lymph nodes, much as niche competition limits their selection in the thymus. The strong perturbations induced by anti-CD3 overcame these niche limitations, in a process dependent on receptors for trophic cytokines, interleukin-2 receptor (IL-2R) and IL-7R. Keywords: Treatment response All gene expression profiles were obtained from highly purified T cell populations sorted by flow cytometry. RNA from 5 - 50 x 104 cells was amplified, labeled, and hybridized to Affymetrix M430v2. Raw data were preprocessed with the RMA algorithm in GenePattern, and averaged expression values were used for analysis.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-22527http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-22527/samples/