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, hi 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).

1 . A method of making a subject non-responsive to one or more antigens, comprising:
 contacting the subject with said one or more antigens and a compound that induces anergy.   
     
     
         2 . A method according to  claim 1 , wherein said compound has an effect on Lck function. 
     
     
         3 . A method according to  claim 2 , wherein said effect is a decrease in Lck function. 
     
     
         4 . A method according to  claim 2 , wherein said function is Lck activity. 
     
     
         5 . A method according to  claim 2 , wherein said function is Lck binding. 
     
     
         6 . A method according to  claim 2 , wherein said function is Lck mediated signaling. 
     
     
         7 . A method according to  claim 2 , wherein said compound effects Lck SH2 activity. 
     
     
         8 . A method according to  claim 1 , wherein the compound is selected from the group consisting of compounds 72, 86, and 241. 
     
     
         9 . A method according to  claim 1 , wherein the antigen is an autoimmune antigen. 
     
     
         10 . A method according to  claim 1 , wherein the mammal is a human. 
     
     
         11 . A method of treating an autoimmune disease in a subject, comprising:
 contacting the subject with an autoimmune antigen and a compound that induces anergy.   
     
     
         12 . A method according to  claim 11 , wherein said compound has an effect Lck function. 
     
     
         13 . A method according to  claim 11 , wherein the compound is selected from the group consisting of compounds 72, 86, and 241. 
     
     
         14 . A method according to  claim 11 , wherein the antigen is selected from a group consisting of achetylcholine receptor, glutamic acid decarboxylase and rheumatoid factor. 
     
     
         15 . A method according to  claim 11 , wherein the mammal is a human. 
     
     
         16 . A method according to  claim 11 , wherein the 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. 
     
     
         17 . A method of transplanting an organ, tissue or cells into a subject, comprising: implanting or injecting the organ, tissue or cells into the subject; and
 administering a compound that induces anergy.   
     
     
         18 . A method according to  claim 17 , wherein the organ is selected from the group consisting of heart, lung, liver, and kidney. 
     
     
         19 . A method according to  claim 17 , wherein the compound has an effect Lck function. 
     
     
         20 . A method according to  claim 17 , wherein the compound is selected from the group consisting of compound 72, 86, and 241. 
     
     
         21 . A method according to  claim 17 , wherein the subject is a human.