Methods and compositions for the generation and maintenance of regulatory T cells
Methods and compositions for generating and maintaining induced regulatory T cells (iTregs) are provided. Methods and compositions for treating an autoimmune disorder, organ transplant rejection, graft versus host disease or allergic or hypersensitivity and inflammation are also provided.
1. A method of generating an induced regulatory T cell (iTreg) comprising the steps of:
a) isolating a CD4 + Foxp3 − naïve T cell;
b) contacting the isolated naïve T cell with PD-L1 and/or PD-L2; and
c) examining the T cell for Foxp3 expression and/or the ability to suppress effector T cell (Teff) activation, wherein Foxp3 expression and/or the ability to suppress Teff activation is indicative of an iTreg.
2. The method of claim 1 , wherein the PD-L is immobilized.
3. The method of claim 2 , wherein the PD-L is immobilized on a bead or a cell.
4. The method of claim 1 , wherein the step of differentiating is performed in the presence of anti-CD3 antibody or anti-CD28 antibody.
5. The method of claim 4 , wherein the anti-CD3 antibody or the anti-CD28 antibody are present on a bead.
6. The method of claim 1 , wherein the step of differentiating is performed in the presence of transforming growth factor-beta (TGF-β).
7. The method of claim 1 , wherein the iTreg expresses forkhead box p3 (Foxp3).
8. The method of claim 1 , wherein the iTreg suppresses effector T cell (Teff) activation.
9. The method of claim 8 , wherein the Teff is a CD4 + Teff.
10. The method of claim 1 , wherein the PD-L antagonizes the Akt signaling pathway.