Use of agents that modulate the interaction between PD-1 and its ligands in the downmodulation of immune responses

Abstract

Disclosed are methods for downmodulating an immune response comprising contacting an immune cell with an agent that modulates the interaction between PD-1 and a PD-1 ligand (e.g., soluble forms of PD-1 or PD-1 ligand or antibodies to PD-1) to thereby modulate the immune response.

1 . A method for downmodulating activation of an immune cell, comprising contacting an immune cell, at the time of contact with antigen, with an agent that modulates signaling via PD-1 to thereby downmodulate activation of an immune cell.  
     
     
         2 . The method of  claim 1 , wherein the agent is selected from the group consisting of: an antibody that transmits an inhibitory signal via PD-1, a soluble form of PD-1, a soluble form of PD-L1, a soluble form of PD-L2, a soluble form of PD-L1 and a soluble form of PD-L2, an antibody to PD-L1, an antibody to PD-L2, an antibody to PD-L1 and an antibody to PD-L2, and a small molecule that transmits an inhibitory signal via PD-1.  
     
     
         3 . The method of  claim 2 , wherein the agent is selected from the group consisting of: a soluble form of PD-L1, a soluble form of PD-L2, and a combination of a soluble form of PD-L1 and PD-L2.  
     
     
         4 . The method of  claim 2 , wherein the antibody that transmits an inhibitory signal via PD-1 is a bivalent antibody that also recognizes an activating receptor.  
     
     
         5 . The method of  claim 1 , wherein the immune cell is a T cell.  
     
     
         6 . The method of  claim 5 , wherein the T cell is a naïve T cell.  
     
     
         7 . The method of  claim 4 , wherein the immune cell is a T cell and the activating receptor is a T cell receptor.  
     
     
         8 . The method of  claim 1 , wherein anergy is induced in the immune cell.  
     
     
         9 . The method of  claim 1 , further comprising contacting the immune cell with an additional agent that downregulates an immune response.  
     
     
         10 . The method of  claim 1 , wherein the step of contacting occurs in vivo.  
     
     
         11 . The method of  claim 1 , wherein the step of contacting occurs in vitro.  
     
     
         12 . A method of downmodulating activation or activity of an activated immune cell from a subject having an autoimmune disorder mediated by activated immune cells, comprising contacting an activated immune cell from the subject with an antibody that binds to PD-1 such that activation or activity of an activated immune cell from a subject having an autoimmune disorder mediated by activated immune cells is downmodulated.  
     
     
         13 . The method of  claim 12 , wherein the immune cell is a T cell.  
     
     
         14 . The method of  claim 12 , wherein the antibody transmits an inhibitory signal via PD-1.  
     
     
         15 . The method of  claim 14 , wherein the antibody that transmits an inhibitory signal via PD-1 is a bivalent antibody that also recognizes the T cell receptor.  
     
     
         16 . The method of  claim 12 , wherein the autoimmune disorder is multiple sclerosis.  
     
     
         17 . The method of  claim 12 , further comprising contacting an immune cell from the subject with an additional agent that downregulates an immune response.  
     
     
         18 . The method of  claim 12 , wherein the step of contacting occurs in vivo.  
     
     
         19 . The method of  claim 12 , wherein the step of contacting occurs in vitro.