Use of Cytokines and Mitogens to Inhibit Pathological Immune Responses

Abstract

The invention is generally related to methods of treating autoimmune diseases, including both antibody-mediated and cell-mediated disorders.

1 . An isolated population of cells comprising at least 50% immunosuppressive regulatory T cells, wherein said immunosuppressive regulatory T cells are CD4+ CD25+. 
     
     
         2 . The isolated population of cells according to  claim 1 , wherein said CD4+ CD25+ immunosuppressive regulatory T cells are antigen specific. 
     
     
         3 . The isolated population according to  claim 2 , wherein said antigen is selected from: an alloantigen and an autoantigen. 
     
     
         4 . The isolated population according to  claim 1 , wherein said CD4+ CD25+ immunosuppressive regulatory T cells are human. 
     
     
         5 . The isolated population according to  claim 4 , wherein said CD4+ CD25+ immunosuppressive regulatory T cells are derived from peripheral blood mononuclear cells (PBMC). 
     
     
         6 . A method of identifying immunosuppressive regulatory T cells in a sample comprising:
 screening T cells in said sample to detect CD4+ CD25+ T cells; and   identifying said detected CD4+ CD25+ T cells as immunosuppressive regulatory T-cells.   
     
     
         7 . The method according to  claim 6 , wherein said method further comprises contacting said sample to a regulatory composition prior to said screening step. 
     
     
         8 . The method according to  claim 7 , wherein said regulatory composition comprises one or more of antigen, cytokines, cells and T cell stimulatory agents. 
     
     
         9 . The method according to  claim 8 , wherein said antigen is selected from: an alloantigen and an autoantigen. 
     
     
         10 . The method according to  claim 8 , wherein said cytokine is selected from: TGF-β, IL-2, and IL-15. 
     
     
         11 . The method according to  claim 8 , wherein said cells are selected from: antigen presenting cells and allogeneic cells. 
     
     
         12 . The method according to  claim 8 , wherein said T cell stimulatory agents are selected from: anti-CD3 antibody, anti-CD28 antibody, anti-CD2 antibody and Concanavalin A. 
     
     
         13 . The method according to  claim 6 , wherein said method further comprises isolating said identified CD4+ CD25+ immunosuppressive regulatory T-cells. 
     
     
         14 . The method according to  claim 13 , wherein said method further comprises expanding said isolated CD4+ CD25+ immunosuppressive regulatory T-cells by contacting said isolated CD4+ CD25+ immunosuppressive regulatory T-cells to a T cell expansion composition. 
     
     
         15 . The method according to  claim 14 , wherein said T cell expansion composition includes one or more of: anti-CD3 antibody, anti-CD28 antibody, anti-CD2 antibody, IL-2, IL-15, antigen presenting cells, antigen and Concanavalin A. 
     
     
         16 . The method according to  claim 6 , wherein said sample is a peripheral blood mononuclear cell (PBMC) sample. 
     
     
         17 . The method according to  claim 6 , wherein said CD4+ CD25+ immunosuppressive regulatory T-cells are human. 
     
     
         18 . A pharmaceutical composition for suppressing a pathological immune response in a subject, wherein said pharmaceutical composition comprises isolated immunosuppressive CD4+ CD25+ regulatory T cells. 
     
     
         19 . The pharmaceutical composition according to  claim 18 , wherein said isolated immunosuppressive CD4+CD25+ regulatory T cells are antigen specific. 
     
     
         20 . The pharmaceutical composition according to  claim 20 , wherein said antigen is selected from: an alloantigen and an autoantigen. 
     
     
         21 . The pharmaceutical composition according to  claim 18 , wherein said immunosuppressive CD4+ CD25+ regulatory T cells are derived from said subject. 
     
     
         22 . The pharmaceutical composition according to  claim 18 , wherein said immunosuppressive CD4+ CD25+ regulatory T cells are derived from a donor.