Method for regulating immune function in primates using the Foxp3 protein

Abstract

Isolated nucleic acid molecules are provided which encode Fkh sf , as well as mutant forms thereof. Also provided are expression vectors suitable for expressing such nucleic acid molecules, and host cells containing such expression vectors. Also provided are pharmaceutical compounds and methods of identifying such compounds that can modulate the immune system. In addition are provided methods for identifying proteins regulated by Scurfin and proteins that induce or inhibit Foxp3 expression.

1 . A method for identifying a compound that modulates the level of expression of scurfin comprising the steps of:
 (a) providing a composition comprising a reporter gene ligated to a scurfin promoter;   (b) contacting the composition with a test compound;   (c) determining the level of reporter gene expression; and   (d) comparing the level of reporter gene expression in (c) with the predetermined level of expression and thereby determining if the test compound modulates the expression of scurfin.   
     
     
         2 . The method of  claim 1 , wherein the level of scurfin expression is decreased. 
     
     
         3 . The method of  claim 1 , wherein the level of scurfin expression is increased. 
     
     
         4 . The method of  claim 1 , wherein the test compound is selected from the group consisting of a monoclonal antibody, a polyclonal antibody, a peptide, a small molecule, an organic molecule, a natural product, a peptide, an oliciosaccharide, a nucleic acid, a lipid, and an antibody or binding fragment thereof. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the test compound is from a library of compounds. 
     
     
         7 . The method of  claim 6 , wherein the library is selected from the group consisting of a random peptide library, a combinatorial library, an oligosaccharide library and a phage display library. 
     
     
         8 . A compound identified according to the method of  claim 1 . 
     
     
         9 . A method for suppressing an immune response in a mammal comprising contacting T cells of the mammal with a compound that increases scurfin expression in the T cell, wherein an immune response is suppressed. 
     
     
         10 . A method for enhancing an immune response in a mammal comprising contacting T cells of the mammal with a compound that decreases scurfin expression in the T cell, wherein an immune response is enhanced. 
     
     
         11 . A method of  claim 9  wherein said immune response is an autoimmune response, and wherein said contacting results from administering said compound to said mammal which increases scurfin expression in said T cells, thereby inhibiting an autoimmune response by the subject and wherein the autoimmune response is selected from the group consisting of Inflammatory Bowel Disease, Multiple Sclerosis, Rheumatoid Arthritis, Psoriasis, Diabetes, and Asthma. 
     
     
         12 . (canceled) 
     
     
         13 . A method of  claim 10  wherein said contacting results from administering to said mammal said compound which decreases scurfin expression, thereby enhancing an immune response to a disease in the subject. 
     
     
         14 . The method of  claim 13 , wherein the disease is selected from the group consisting of AIDS and cancer. 
     
     
         15 . A method of  claim 9  wherein said immune response contributes to graft versus host disease wherein said contacting comprises administering to the mammal said compound that increases scurfin expression in said T cells, thereby inhibiting graft versus host disease in the subject. 
     
     
         16 . A method of  claim 9  wherein said method comprises:
 (a) isolating T cells from said mammal;   (b) transducing the T cells with the scurfin gene;   (c) expanding the transduced T cells; and   (d) reintroducing the transduced T cells into said mammal,   wherein an autoimmune response in the patient is inhibited.   
     
     
         17 . The method of  claim 16  wherein the T cells are CD4+CD25+ regulatory T cells. 
     
     
         18 . The method of  claim 16 , wherein the autoimmune disease is selected from the group consisting of Inflammatory Bowel Disease, Multiple Sclerosis, Rheumatoid Arthritis, Psoriasis, Diabetes, and Asthma. 
     
     
         19 . The method of  claim 16 , wherein the transduction vector is a retroviral vector. 
     
     
         20 . A method of  claim 10  wherein said method comprises:
 (a) isolating T cells from said mammal;   (b) transfecting the T cells with a compound that inhibits scurfin expression;   (c) expanding the transfected T cells; and   (d) reintroducing the transfected T cells into said mammal, wherein an immune response to a disease in the patient is enhanced.   
     
     
         21 . The method of  claim 20  wherein the compound is an anti-sense molecule. 
     
     
         22 . The method of  claim 20 , wherein the disease is selected from the group consisting of AIDS and cancer.