Method for ex-vivo expansion of regulatory t cells with enhanced suppressive function for clinical application in immune mediated diseases

Abstract

The invention provides methods for the ex-vivo expansion of CD4+CD25+ Tregs. The invention provides a method for producing ex vivo expanded Tregs that may be used to inhibit unwanted human immune responses against self-antigens or allergens. Additionally, the ex vivo expanded Tregs may provide treatment for inflammatory/automimmune diseases.

1 . A method comprising: a) obtaining a population of T cells from an individual with an immune-mediated disease selected from Systemic Lupus Erythematous, Multiple Sclerosis, asthma, Rheumatoid Arthritis, Crohn's Disease, or Ulcerative Colitis; b) isolating and purifying from the T cell population a subpopulation of CD4+CD25+ Tregs; and c) expanding the Treg cells of the subpopulation, wherein the expanded Treg cells exhibit enhanced suppressive activity compared to a population of freshly purified, unexpanded Tregs from the individual. 
     
     
         2 . The method of  claim 1 , wherein the expansion is between about 100 to 1,000 fold. 
     
     
         3 . The method of  claim 1 , wherein the expansion was carried out for a period of about 3 weeks. 
     
     
         4 . A method of treating an individual with immune-mediated disease, the method comprising: a) obtaining a population of T cells from an individual with an immune-mediated disease selected from Systemic Lupus Erythematous, Multiple Sclerosis, asthma, Rheumatoid Arthritis, Crohn's Disease, or Ulcerative Colitis; b) isolating and purifying from the T cell population a subpopulation of CD4+CD25+ Tregs; c) expanding the Treg cells of the subpopulation; and d) administering a portion of the CD4+CD25+ regulatory T cells to a human being treated for the immune-mediated disease. 
     
     
         5 . The method of  claim 4 , wherein the immune-mediated disease is Systemic Lupus Erythematous. 
     
     
         6 . The method of  claim 4 , wherein the immune-mediated disease is Multiple Sclerosis. 
     
     
         7 . The method of  claim 4 , wherein the immune-mediated disease is asthma, Rheumatoid Arthritis. 
     
     
         8 . The method of  claim 4 , wherein the immune-mediated disease is Rheumatoid Arthritis. 
     
     
         9 . The method of  claim 4 , wherein the immune-mediated disease is Crohn's Disease. 
     
     
         10 . The method of  claim 4 , wherein the immune-mediated disease is Ulcerative Colitis.