Induction of immunological tolerance

Abstract

A method of creating tolerance to transplanted cells, tissue, or organs without the need for continuous immunosuppression. A tolerizing dose of a cell or tissue within a membrane structure is implanted into a patient. Once the patient becomes tolerant to the cell or tissue, a tissue or organ is implanted which will no longer be recognized as foreign matter. The method makes animal organs practical for human use, prevents autoimmune destruction as well as immune rejection. It has applications in treatment and prevention of many mammalian diseases.

What is claimed is:  
     
         1 . A method of creating immunological tolerance to foreign cells, tissues or organs in a mammal, comprising the step of implanting in said mammal a tolerizing dose of corresponding foreign cells or tissue which shed antigens contained in or on said foreign cells tissues or organs, said corresponding foreign cells or tissue being encapsulated in a biologically-compatible permselective membrane.  
     
     
         2 . The method of  claim 1 , further comprising the step of administering to said mammal a curative dose of said foreign cells, tissue or organs.  
     
     
         3 . The method of  claim 2 , wherein said curative dose of said foreign cells, tissues or organs are unencapsulated.  
     
     
         4 . The method of  claim 1 , wherein the mammal is a human, canine or feline.  
     
     
         5 . The method of  claim 1 , wherein said tolerizing cells are insulin-secreting cells.  
     
     
         6 . The method of  claim 5 , wherein said insulin-secreting cells are pancreatic islet cells.  
     
     
         7 . The method of  claim 1 , wherein said membrane comprises polyethylene glycol.  
     
     
         8 . The method of  claim 2 , wherein said curative dose is between one and two orders of magnitude greater than said tolerizing dose.  
     
     
         9 . The method of  claim 2 , wherein said tolerizing and curative doses are from the same species as said mammal.  
     
     
         10 . The method of  claim 2 , wherein said tolerizing and curative doses are from a species different from said individual.  
     
     
         11 . The method of  claim 10 , wherein said tolerizing and curative doses are porcine.  
     
     
         12 . The method of  claim 2 , further comprising the step of administering one or more anti-inflammatory agents to said mammal prior to, at the same time as, or subsequent to administration of said curative dose.  
     
     
         13 . The method of  claim 1 , wherein the membrane has a molecular weight cutoff of about 150 kDa or less.  
     
     
         14 . The method of  claim 9 , wherein the membrane has a pore size of about 0.4 μm or less.  
     
     
         15 . The method of  claim 10 , wherein the membrane has a molecular weight cutoff of about 150 kDa or less.  
     
     
         16 . The method of  claim 14 , wherein the membrane has a pore size of about 0.2 μm or less.  
     
     
         17 . The method of  claim 1 , wherein said tolerizing step is subcapsular, subcutaneous, intraperitoneal or intraportal.  
     
     
         18 . The method of  claim 2 , wherein said curative step is intraperitoneal, intraportal or subcutaneous.  
     
     
         19 . The method of  claim 1 , wherein said tolerizing dose is administered incrementally.  
     
     
         20 . A method of treating diabetes in a mammal in need thereof, comprising the steps of: 
 implanting in said mammal a tolerizing dose of foreign insulin-secreting cells encapsulated in a biologically compatible permselective membrane; then    administering to said mammal a curative dose of corresponding unencapsulated insulin-secreting cells.    
     
     
         21 . The method of  claim 20 , wherein said mammal is a human, canine or feline.  
     
     
         22 . The method of  claim 20 , wherein said tolerizing dose is one to two orders of magnitude less than said curative dose.  
     
     
         23 . The method of  claim 20 , wherein said insulin-secreting cells are pancreatic islet cells.  
     
     
         24 . The method of  claim 20 , wherein said membrane comprises polyethylene glycol.  
     
     
         25 . The method of  claim 20 , wherein said mammal and said insulin-secreting cells are from the same species.  
     
     
         26 . The method of  claim 20 , wherein said mammal and said insulin-secreting cells are from different species.  
     
     
         27 . method of  claim 26 , wherein said tolerizing and curative doses are porcine.  
     
     
         28 . The method of  claim 26 , further comprising the step of administering one or more anti-inflammatory agents to said mammal prior to, at the same time as, or subsequent to administration of said curative dose.  
     
     
         29 . The method of  claim 20 , wherein said membrane has a molecular weight cutoff of about 150 kDa or less.  
     
     
         30 . The method of  claim 25 , wherein said membrane has a pore size of less than about 0.4 μm.  
     
     
         31 . The method of  claim 26 , wherein said membrane has a molecular weight cutoff of about 150 kDa or less.