Compositions and methods for diminishing an immune response

Abstract

The invention is based upon the discovery that T regulatory type 1 (Tr1) cells express particular cell surface markers that allow for their selection, enrichment, isolation, purification and administration. The ability to use the particular markers described herein to select, enrich, isolate, purify and administer Tr1 cells allows for improved methods of Tr1 therapies for treating a wide variety of diseases and disorders.

1 . A method of treating or preventing a disease or disorder associated with an immune response in a subject in need thereof, the method comprising administering to the subject an effective amount of CD4+CD49+LAG-3+ Tr1 cells. 
     
     
         2 . The method of  claim 1 , wherein the cells are CD45RA−. 
     
     
         3 . The method of  claim 1 , wherein the disease or disorder is an inflammatory disease or disorder. 
     
     
         4 . The method of  claim 1 , wherein the disease or disorder is an autoimmune disease or disorder. 
     
     
         5 . The method of  claim 1 , wherein the disease or disorder is associated with transplantation. 
     
     
         6 . The method of  claim 1 , wherein the disease or disorder is at least one selected from the group consisting of allergy, asthma, inflammatory bowel disease, autoimmune entheropathy, Addision's disease, alopecia areata, ankylosing spondylitis, autoimmune hepatitis, autoimmune parotitis, Crohn's disease, diabetes mellitus, dystrophic epidermolysis bullosa, epididymitis, glomerulonephritis, Graves' disease, Guillain-Barr syndrome, Hashimoto's disease, hemolytic anemia, systemic lupus erythematosus, multiple sclerosis, myasthenia gravis, pemphigus vulgaris, psoriasis, rheumatic fever, rheumatoid arthritis, sarcoidosis, scleroderma, Sjogren's syndrome, spondyloarthropathies, thyroiditis, vasculitis, vitiligo, myxedema, pernicious anemia, ulcerative colitis, cell and organ transplant rejection and graft versus host disease. 
     
     
         7 . The method of  claim 1  for treating an inflammatory disease or disorder, an autoimmune disease or disorder, and a disease or disorder associated with transplantation in a subject in need thereof. 
     
     
         8 . A method of inhibiting alloreactive T cells in a subject in need thereof, the method comprising contacting the alloreactive T cells with an effective amount of CD4+CD49+LAG-3+ Tr1 cells. 
     
     
         9 . The method of  claim 8 , wherein the cells are CD45RA−. 
     
     
         10 . A method for preventing or treating an immune response in a subject in need thereof, said method comprising administering to said subject prior to onset of the immune response an effective amount of CD4 + CD49 + LAG-3 +  Tr1 cells to prevent said response. 
     
     
         11 . The method of  claim 10 , wherein the cells are CD45RA−. 
     
     
         12 . The method of  claim 10 , wherein the immune response is an alloreactive response. 
     
     
         13 . The method of  claim 10 , wherein the immune response is an inflammatory response. 
     
     
         14 . The method of  claim 10 , wherein the immune response is an autoimmune response.