Targeted expansion of qa-1-peptide-specific regulatory cd8 t cells to ameliorate arthritis

Abstract

Nanoparticles to treat autoimmune diseases and HIV infection are provided. The nanoparticles comprise a biocompatible polymer and a complex, wherein the complex is a major histocompatibility complex (MHC) class I antigen E (HLA-E) linked to a peptide, and wherein the HLA-E-peptide complex is linked to the surface of the nanoparticle. The present invention also relates to methods for treating autoimmune diseases and HIV infection.

We claim: 
     
         1 - 32 . (canceled) 
     
     
         33 . A method for treating a disease or infection, comprising:
 contacting dendritic cells isolated from a subject with a self-peptide to generate self-peptide-loaded dendritic cells; and   administering the self-peptide-loaded dendritic cells to the subject in an amount effective to ameliorate a symptom of the disease or infection.   
     
     
         34 . The method of  claim 33 , wherein the self-peptide is selected from the group consisting of Hsp60 p216 , B7sp, and FL9. 
     
     
         35 . The method of  claim 33 , wherein the dendritic cells are contacted with the self-peptide for 2 or more hours to generate the self-peptide-loaded dendritic cells. 
     
     
         36 . The method of  claim 33 , wherein the disease comprises an autoimmune disease. 
     
     
         37 . The method of  claim 36 , wherein the autoimmune disease is selected from the group consisting of systemic lupus erythematosus, chronic graft versus host disease, rheumatoid arthritis, insulin-dependent diabetes mellitus, multiple sclerosis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Graves disease, Crohn's disease, Waldenstrom's macroglobulinemia, hyperviscosity syndrome, monoclonal gammopathy of undetermined origin, POEMS syndrome, myeloma, macroglobulinemia, and cold agglutinin disease. 
     
     
         38 . The method of  claim 33 , wherein the infection comprises an HIV infection. 
     
     
         39 . The method of  claim 33 , wherein the contacting comprises mixing the self-peptide with the dendritic cells or expressing the self-peptide from a recombinant nucleic acid in the dendritic cells. 
     
     
         40 . The method of  claim 33 , wherein the dendritic cells bind the self-peptide from a medium containing the dendritic cells and the self-peptide or process the self-peptide intra-cytoplasmically before presenting the peptide, to produce the self-peptide-loaded dendritic cells. 
     
     
         41 . The method of  claim 33 , wherein administering the self-peptide-loaded dendritic cells to the subject induces expansion in the subject of CD8 T cells specific for the self-peptide. 
     
     
         42 . The method of  claim 41 , wherein the CD8 T cells comprise CD8 Treg cells. 
     
     
         43 . A method for treating an autoimmune disease, comprising:
 contacting dendritic cells isolated from a subject with an Hsp60 p216 , B7sp, or FL9 self-peptide to generate Hsp60 p216 -, B7sp-, or FL9-loaded dendritic cells; and   administering the loaded dendritic cells to the subject.   
     
     
         44 . The method of  claim 43 , wherein the autoimmune disease is selected from the group consisting of systemic lupus erythematosus, chronic graft versus host disease, rheumatoid arthritis, insulin-dependent diabetes mellitus, multiple sclerosis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Graves disease, Crohn's disease, Waldenstrom's macroglobulinemia, hyperviscosity syndrome, monoclonal gammopathy of undetermined origin, POEMS syndrome, myeloma, macroglobulinemia, and cold agglutinin disease. 
     
     
         45 . The method of  claim 43 , wherein the dendritic cells are contacted with the self-peptide for about 22-24 hours to generate the Hsp60 p216 -, B7sp-, or FL9-loaded dendritic cells. 
     
     
         46 . The method of  claim 43 , wherein administering the Hsp60 p216 , B7sp, or FL9-peptide-loaded dendritic cells to the subject causes expansion and/or activation in the subject of CD8 T cells that bind the peptide. 
     
     
         47 . A method for expanding CD8 T cells specific for a self-peptide in a first subject, comprising:
 pulsing dendritic cells isolated with an Hsp60 p216 , B7sp, or FL9 self-peptide to generate Hsp60 p216 -, B7sp-, or FL9-loaded dendritic cells; and   vaccinating the subject with the Hsp60 p216 -, B7sp-, or FL9-loaded dendritic cells to expand and/or activate CD8 T cells in the subject specific for the self-peptide.   
     
     
         48 . The method of  claim 47 , wherein the dendritic cells pulsed with the self-peptide are from the first subject. 
     
     
         49 . The method of  claim 47 , wherein the dendritic cells pulsed with the self-peptide are from a second subject. 
     
     
         50 . The method of  claim 47 , wherein the vaccinating ameliorates a symptom of an autoimmune disease selected from the group consisting of systemic lupus erythematosus, chronic graft versus host disease, rheumatoid arthritis, insulin-dependent diabetes mellitus, multiple sclerosis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Graves disease, Crohn's disease, Waldenstrom's macroglobulinemia, hyperviscosity syndrome, monoclonal gammopathy of undetermined origin, POEMS syndrome, myeloma, macroglobulinemia, and cold agglutinin disease. 
     
     
         51 . The method of  claim 47 , wherein the first subject has symptoms of an autoimmune disease and the vaccinating suppresses pathogenic CD4 cells in the subject and/or suppresses disease progression. 
     
     
         52 . A method for treating an autoimmune disease, comprising administering to a subject:
 a. dendritic cells loaded with Hsp60 p216 , B7sp, or FL9 self-peptide; and   b. nanoparticles comprising a biocompatible polymer linked to a complex on a surface of the nanoparticle, the complex comprising a MHC HLA-E linked to a Hsp60 p216 , B7sp, or FL9 self-peptide.