Method for In Vivo Expansion of T Regulatory Cells

Abstract

Compositions specific for TNF-receptor superfamily member 25 (TNFRSF25, DR3) modulate the immune response by regulating T regulatory cells.

1 . A method of regulating an immune response in vivo, comprising:
 administering to a subject in need thereof, an agonist of tumor necrosis factor superfamily receptor 25 (TNFRSF25);   wherein the TNFRSF25 agonist modulates regulatory T cell (Treg) proliferation.   
     
     
         2 . The method of  claim 1 , wherein the TNFRSF25 agonist stimulates signaling of TNFRSF25 and induces proliferation of CD4 + FoxP3 +  cells in the subject as compared to a normal, healthy control. 
     
     
         3 . The method of  claim 1 , wherein the Treg cell is identified by expression of markers comprising: TNFR25, OX40, GITR or 4-1BB. 
     
     
         4 . The method of  claim 3 , wherein the Treg cell differential express high levels of TNFR25 as compared to conventional T cells (Tconv; CD4 + FoxP3 − ). 
     
     
         5 . The method of  claim 2 , wherein the at least one agent is administered to a patient in a therapeutically effective dose as determined by the proliferation of Treg CD4 + FoxP3 +  cells in a patient. 
     
     
         6 . The method of  claim 1 , wherein the TNFRSF25 agonist is administered to a patient in a plurality of therapeutically effective doses. 
     
     
         7 . The method of  claim 6 , wherein the plurality of therapeutically effective doses of the at least one agent are administered to a patient and abrogate suppressive activity of the Treg cells as measured by Treg production of suppressor factors, cell proliferation assays, flow cytometry or immunoassays. 
     
     
         8 . The method of  claim 1 , wherein the TNFRSF25 agonist is an antibody, an aptamer, a ligand, a small molecule, a peptide, a protein, an oligonucleotide, a polynucleotide, or an organic or inorganic molecule. 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 8 , wherein the TNFRSF25 agonist is an antibody specific for TNFRSF25. 
     
     
         11 - 33 . (canceled)