Regulatory T cell PD-1 modulation for regulating T cell effector immune responses
The present invention is based, in part, on the identification of methods of modulating PD-1 expression and/or activity in regulatory T cells (Tregs) to thereby regulate effector immune responses in effector T cells (Teffs).
1. A method for increasing suppression of effector T cells (Teffs) by regulatory T cells (Tregs), comprising a) inhibiting or blocking the expression of PD-1 in Tregs; and b) contacting the Tregs with Teffs, thereby increasing suppression of the Teffs by the Tregs.
2. The method of claim 1 , wherein the Tregs are isolated from a subject, and the PD-1 expression is inhibited or blocked in the Tregs in vitro or ex vivo.
3. The method of claim 1 , wherein the Tregs contact the Teffs in vitro or ex vivo, or in vivo.
4. The method of claim 3 , wherein the Tregs and/or Teffs are administered to a subject.
5. The method of claim 1 , wherein the Tregs are contacted with at least one agent that inhibits or blocks the expression of PD-1, wherein the at least one agent is a nucleic acid molecule that blocks PD-1 transcription or translation.
6. The method of claim 3 , wherein the Tregs are administered to a subject having a disorder in need of increased suppression of Teffs by the Tregs, and the disorder is selected from the group consisting of autoimmune disorder, allergic disorder, hypersensitivity disorder, graft-versus-host disease (GVHD), solid organ transplantation rejection, vasculitis, systemic lupus erythematosus (SLE), type 1 diabetes (T1D), multiple sclerosis (MS), psoriasis, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and allergic asthma, ankylosing spondylitis (AS), and giant cell arteritis (GCA).
7. The method of claim 3 , wherein the Tregs are administered to a subject receiving a therapy in need of increased suppression of Teffs by the Tregs, wherein the therapy is selected from the group consisting of adoptive cell therapy, solid organ transplantation, stem cell therapy, and gene therapy.