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3. What kinds of chemicals are released by the Tregs to suppress Teffs?
(alt. modes of of action) - It has been reported that Foxp3+ Treg cells exert suppression by cell contact–dependent mechanisms (for example, functional modulation by means of CD39, CD73 and LAG-3, or killing of APCs or responder T cells by means of granzyme and perforin) as well as mechanisms mediated by soluble factors (for example, secretion of immunosuppressive cytokines such as IL-10, TGF-β, IL-35 and galectin-1, or deprivation of cytokines (for example, IL-2) necessary for the expansion and/or survival of responder T cells65, 66, 67). It is thus likely that several mechanisms or modes of suppression may operate synergistically and in a complementary manner and that each mechanism contributes to suppression to a particular extent and under a certain condition. "
- IL-10, IL-9, adenosine
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- CTLA-4 (protein receptor on surface) http://www.nature.com/ni/journal/v11/n1/fig_tab/ni.1818_F2.html (highly expressed narturally; suppression directly leads to autoimmune disorder)
- Galectin 1, 10 ?
4. How can we modify MHC (or other APC surface protein) to release the chemicals normally released by Tregs when a Teff successfully binds MHC?
- FoxP3 is transcription factor centrally responsible for Treg function: absence of it leads to IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome) (a fancy way of saying your body will attack itself on all fronts and life will absolutely suck)
- "It is thus likely that several mechanisms or modes of suppression may operate synergistically and in a complementary manner and that each mechanism contributes to suppression to a particular extent and under a certain condition. " (super interesting imo) we all carry diabetogenic t cells controlled by tregs; malfunction of foxp3 makes us all instant type 1 diabetics
4. How can we modify MHC (or other APC surface protein) to release the chemicals normally released by Tregs when a Teff successfully binds MHC?
- Link to kit for synthetic regulated secretion pathway - http://www.ariad.com/pdf/Reg_Secretion-Aggregation.pdf
Other New, Relevant Information:
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