Materials and methods for the development of an antigen-specific immune non-responsiveness state

Abstract

The present invention provides materials and methods for making a subject non-responsive to an antigen. Methods of the invention may comprise contacting the subject with the antigen and a compound that induces anergy. In some embodiments, the antigen may be an autoimmune antigen, examples of which include, but are not limited to acetylcholine receptor for myasthenia gravis, glutamic acid decarboxylase for type I diabetes mellitus and rheumatoid factor in rheumatoid arthritis. In some embodiments, the present invention provides a method of transplanting an organ, tissue, or cells into a subject (e.g. a mammal such as a human).

What is claimed is: 
     
         1 . A method of making a subject non-responsive to an antigen, comprising:
 administering the antigen to the subject; and   administering an effective amount of a small molecule compound to the subject;   wherein the small molecule compound prevents T cell activation by interfering with the activity of lymphocyte-specific protein tyrosine kinase (Lck).   
     
     
         2 . The method of  claim 1 , wherein the effective amount of the small molecule compound is administered before, simultaneously with, and/or after administration of the antigen. 
     
     
         3 . The method of  claim 1 , wherein the antigen is an autoimmune antigen selected from acetylcholine receptor for myasthenia gravis, glutamic acid decarboxylase for type I diabetes mellitus and rheumatoid factor in rheumatoid arthritis. 
     
     
         4 . The method of  claim 1 , wherein the small molecule compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The method of  claim 1 , wherein the effective amount is from about 0.1 mg/kg body weight to about 100 mg/kg body weight. 
     
     
         6 . The method of  claim 1 , wherein the effective amount is 1 mg/kg body weight. 
     
     
         7 . A method of treating an autoimmune disease in a mammalian subject, comprising:
 administering an autoimmune antigen to the subject; and   administering an effective amount of a small molecule compound to the subject;   wherein the small molecule compound prevents T cell activation by interfering with the activity of lymphocyte-specific protein tyrosine kinase (Lck).   
     
     
         8 . The method of  claim 7 , wherein the effective amount of the small molecule compound is administered before, simultaneously with, and/or after administration of the antigen. 
     
     
         9 . The method of  claim 7 , wherein the antigen is an autoimmune antigen selected from acetylcholine receptor for myasthenia gravis, glutamic acid decarboxylase for type I diabetes mellitus and rheumatoid factor in rheumatoid arthritis. 
     
     
         10 . The method of  claim 7 , wherein the small molecule compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         11 . The method of  claim 7 , wherein the effective amount is from about 0.1 mg/kg body weight to about 100 mg/kg body weight. 
     
     
         12 . The method of  claim 7 , wherein the effective amount is 1 mg/kg body weight. 
     
     
         13 . The method of  claim 7 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, glomerulonephritis, Hashimoto's thyroiditis, multiple sclerosis, systemic lupus erythematosus, myasthenia gravis, autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, type 1 diabetes, Chrohn's disease, Grave's disease and celiac disease. 
     
     
         14 . A method of transplanting an organ, tissue or cells into a mammalian subject, comprising:
 implanting the organ, tissue or cells into the subject; and   administering an effective amount of a small molecule compound to the subject;   wherein the small molecule compound prevents T cell activation by interfering with the activity of lymphocyte-specific protein tyrosine kinase (Lck).   
     
     
         15 . The method of  claim 14 , wherein the effective amount of the small molecule compound is administered before, simultaneously with, and/or after implanting the organ, tissue or cells. 
     
     
         16 . The method of  claim 14 , wherein the small molecule compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         17 . The method of  claim 14 , wherein the effective amount is from about 0.1 mg/kg body weight to about 100 mg/kg body weight. 
     
     
         18 . The method of  claim 14 , wherein the effective amount is 1 mg/kg body weight.