Systematic name M7709
Brief description Genes down-regulated in T reg following anti-CD3 in vivo treatment versus control.
Full description or abstract Treatment 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.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 20679403   Authors: Nishio J,Feuerer M,Wong J,Mathis D,Benoist C
Exact source GSE22527_3555_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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