Compositions and methods for the prevention and treatment of autoimmune conditions

Abstract

The methods include selectively reducing or expanding T cells according to the antigenic specificity of the T cells. Therefore, the present invention can be used to reduce or eliminate pathogenic T cells that recognize autoantigens, such as beta cell specific T cells. As such, the present invention can be used to prevent, treat or ameliorate autoimmune diseases such as IDDM. Furthermore, the present invention can be used to expand desirable T cells, such as antipathogenic T cells to prevent, treat and/or ameliorate autoimmune diseases.

What is claimed is: 
     
         1 . A method of treating an autoimmune disorder in a subject in need thereof comprising administering to the subject a nanoparticle complex comprising antigen-MHC complexes operatively coupled to a non-liposomal nanoparticle core in an amount sufficient to expand anti-pathogenic autoreactive T cells; wherein the non-liposomal nanoparticle core has a diameter of less than 1 μm; and wherein the ratio of antigen-MHC complexes operatively coupled to the non-liposomal nanoparticle core is from about 10:1 to about 1000:1. 
     
     
         2 . The method of  claim 1 , wherein the non-liposomal nanoparticle core further comprises an outer layer, and wherein the antigen-MHC complexes are operatively coupled to the non-liposomal nanoparticle core or the outer layer. 
     
     
         3 . The method of  claim 2 , wherein the outer layer comprises polyethylene glycol. 
     
     
         4 . The method of  claim 1  or  2 , wherein the non-liposomal nanoparticle core comprises a metal, a metal oxide, a metal sulfide, a metal selenide, a magnetic material, or a polymer. 
     
     
         5 . The method of  claim 4 , wherein the metal is gold or iron. 
     
     
         6 . The method of  claim 4 , wherein the metal oxide is iron oxide. 
     
     
         7 . The method of  claim 1  or  2 , wherein the antigen is derived from an autoantigen, an autoantigen epitope, or a mimic thereof. 
     
     
         8 . The method of  claim 1  or  2 , wherein the antigen-MHC complexes comprise the same or different autoantigens or antigens. 
     
     
         9 . The method of  claim 1  or  2 , wherein the antigen-MHC complexes comprise the same or different MHC proteins. 
     
     
         10 . The method of  claim 1  or  2 , wherein the MHC component of the antigen-MHC complexes is a classical or non-classical MHC class I protein. 
     
     
         11 . The method of  claim 10 , wherein the classical or non-classical MHC class I protein comprises all or part of a HLA-A or CD-1 protein. 
     
     
         12 . The method of  claim 10 , wherein the classical or non-classical MHC class I component comprises all or part of a HLA-A protein. 
     
     
         13 . The method of  claim 10 , wherein the classical or non-classical MHC class I component comprises all or part of a HLA-A*0201 WIC class I protein. 
     
     
         14 . The method of  claim 1  or  2 , wherein the MHC component of the antigen-MHC complexes is a classical or non-classical MHC class II protein. 
     
     
         15 . The method of  claim 14 , wherein the classical or non-classical MHC class II protein comprises all or part of a HLA-DR, HLA-DQ, or HLA-DP protein. 
     
     
         16 . The method of  claim 1  or  2 , wherein the WIC component of the antigen-MHC complexes is a non-classical MHC class I protein or a non-classical MHC class II protein. 
     
     
         17 . The method of  claim 1  or  2 , wherein the antigen of the antigen-MHC complexes is covalently coupled to the WIC component. 
     
     
         18 . The method of  claim 1  or  2 , wherein the antigen-MHC complexes are covalently coupled to the non-liposomal nanoparticle core or the outer layer via a linker. 
     
     
         19 . The method of  claim 18 , wherein the linker is ethylene glycol. 
     
     
         20 . The method of  claim 1  or  2 , wherein the anti-pathogenic autoreactive T cells are CD4 +  or CD8 +  T cells. 
     
     
         21 . The method of  claim 1  or  2 , wherein the administration of the nanoparticle complex is prior to the onset of clinical symptoms of the autoimmune disorder. 
     
     
         22 . The method of  claim 1  or  2 , wherein the administration of the nanoparticle complex is after the onset of clinical symptoms of the autoimmune disorder. 
     
     
         23 . The method of  claim 1  or  2 , wherein the autoimmune disorder is selected from the group consisting of Pre-Diabetes, Juvenile Onset Diabetes Mellitus, Adult Onset Diabetes Mellitus, Sjogren's Disease, Crohn's Disease, Ulcerative Colitis, Inflammatory Bowel Disease, Autoimmune Hepatitis, Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis, Uveitis, Rheumatoid Arthritis, Asthma, Multiple Sclerosis, Pemphigus Folliaceus, Pemphigus Vulgaris, Psoriasis, Systemic Lupus Erythematosus, Celiac Disease, Chronic Obstructive Pulmonary Disease, Emphysema, Atherosclerosis, and Scleroderma. 
     
     
         24 . The method of  claim 1  or  2 , further comprising assessing the presence or quantity of the anti-pathogenic autoreactive T cell population. 
     
     
         25 . The method of  claim 24 , wherein assessing the presence or quantity of the anti-pathogenic autoreactive T cell population comprises:
 a) isolating a sample from the subject suspected of containing the population of antigen-specific T cells;   b) contacting the sample with an effective amount of a tetramer complex comprising the antigen-MHC complexes; and   c) detecting and quantifying the number of antigen-specific T cells bound to the tetramer complex.   
     
     
         26 . The method of  claim 25 , wherein the step of quantifying the number of antigen-specific T cells of step c) comprises the use of flow cytometry. 
     
     
         27 . The method of  claim 25 , wherein the step of quantifying the number of antigen-specific T cells of step c) comprises the use of ELISPOT.