Regulatory T cells

Metabolic disruption
1. IL-2 deprevation
  1. Due to high expression of CD25
  2. suppress both IL-2 mRNA and protein production by Teff
2. cAMP
  1. formed in Tregs and diffuses through gap junctions
    1. Potent inhib 2nd messenger of Teff
3. Ectoenzymes - CD39 & CD73
  1. Degrade ATP
    1. ↑ adenosine (intra and extracellular)
      1. A2A rec on Teff ∴ immunospression
        ↑ iTreg via reduction of IL-6 and increase of TGFb
      2. Promotes toleregenic phenotype of DC (Ernst)
        Diagolo 2007
4. High expression HO-1
  1. Heam degradation ∴ suppresive CO
    1. byung Min 2005
      1. HO-1 inhbits IL-2 production in Teff
      2. HO-1 KO results in Th1 shift
  2. induced by Foxp3
5. Galectin-10
  1. Enter text here
Cytolysis
1. Granzyme A/B
  1. Serine proteases cleave and activate caspases
    1. apoptosis of Teff
    2. Teff that over express the GB inhibitor SPI6 are resistant to Treg suppression (Noelle)
2. TRAIL-DR5 mediated apoptosis
3. Galectin-1 upreg in hu & mu Tregs
Dendritic Cells
1. ↓ maturation via LAG3
  1. ITAM mediated inhib signalling via FcyRy. ERK mediated SHP1 recruitment
    1. Silencing of signal transduction
      1. ↓ Teff activation
  2. CD4 homologue, bings w/ high aff to MHC II
    1. Tregs may also express MHCII to bind with LAG3/CD4 on Teff in order to supress activation
      1. Baecher Allen 2006
2. CTLA4
  1. Interaction w/ CD80/86
    1. IDO induction in DC
      1. Degrades tryptophan
        Essential for Tc growth and survival
        Release of pro-apoptopic metabolites
    2. Restricts CD28 binding
      1. Co-stim required for Tc activation (w/ TCR)
        Teff ligand sequestration
    3. Endocysis of whole complex by Tregs
      1. ↓ APC ligands ∴ stimulatory capacity
  2. ↑ TGFb transcription
3. intravital microscopy shows direct interactions
4. neuropilin-1 - promotes prolonged DC/Treg interactions
  1. preferncial binding of Tregs over Teff
Cytokines
1. IL-10
  1. Signal for iTregs
2. TGFb
  1. autocrine signalling for survival
  2. Direct suppression of Teff
    1. TGFb resistant Teff cannot be controlled by Tregs in IBD mouse models
  3. Membrane tethered TGFb - controls CD8 infiltration to pancreatic ilets
    1. Supresses Bc IgG production
    2. Nakamura 2001
    3. suppresed NK cells via NKG2D
  4. soluable
3. IL-35
  1. Heterodimeric protein preferentially expressed in Tregs
  2. Collison 2007
4. IL-9
  1. recruits & activates mast cells
    1. essential regulatory mediators in allograft tolerance

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Regulatory T cells

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	Created by Livvi Harris over 10 years ago