Specific tolerance in transplantation

Abstract

In general, the invention features, a method of inducing tolerance in a recipient mammal, e.g., a human, of a first species to a tissue obtained from a mammal, e.g., a swine, e.g., a miniature swine, of a second species, which tissue expresses an MHC antigen, including inserting DNA encoding an MHC antigen of the second species into a bone marrow hematopoietic stem cell from the recipient mammal, and allowing the MHC antigen encoding DNA to be expressed in the recipient.

1 . A method of inducing tolerance in a recipient mammal of a first species to a tissue obtained from a mammal of a second species, which tissue expresses an MHC antigen, said method comprising 
 inserting DNA encoding an MHC antigen of said second species into a bone marrow hematopoietic stem cell from said recipient mammal, and    allowing said MHC antigen encoding DNA to be expressed in the recipient.    
     
     
         2 . The method of  claim 1 , wherein said cell is removed from said recipient mammal prior to said insertion and returned to said recipient mammal after said insertion.  
     
     
         3 . The method of  claim 1 , wherein said recipient is a human.  
     
     
         4 . The method of  claim 1 , wherein said mammal is a swine.  
     
     
         5 . The method of  claim 4 , wherein said swine is a miniature swine.  
     
     
         6 . The method of  claim 1 , wherein said DNA is obtained from the individual mammal from which said tissue is obtained.  
     
     
         7 . The method of  claim 1 , wherein said DNA is obtained from an individual mammal which is syngeneic to the individual mammal from which said tissue is obtained.  
     
     
         8 . The method of  claim 1 , wherein said DNA is obtained from an individual mammal which is MHC identical to the individual mammal from which said tissue is obtained.  
     
     
         9 . The method of  claim 1 , wherein said DNA comprises an MHC class I gene.  
     
     
         10 . The method of  claim 1 , wherein said DNA comprises an MHC class II gene.  
     
     
         11 . The method of  claim 1 , wherein said DNA is inserted into said cell by transduction.  
     
     
         12 . The method of  claim 11 , wherein said DNA is inserted into said cell by a retrovirus.  
     
     
         13 . The method of  claim 12 , wherein said DNA is recipient is a human and said retrovirus is a Moloney-based retrovirus.  
     
     
         14 . A method of inducing tolerance in a recipient mammal to a tissue obtained from a donor mammal of the same species, which tissue expresses an MHC antigen, said method comprising 
 inserting DNA encoding an MHC antigen of said donor into a bone marrow hematopoietic stem cell from said recipient mammal, and    allowing said MHC antigen encoding DNA to be expressed in the recipient.    
     
     
         15 . The method of  claim 14 , wherein said cell is removed from said recipient prior to said insertion and returned to said recipient after said insertion.  
     
     
         16 . The method of  claim 14 , wherein said recipient is a human.  
     
     
         17 . The method of  claim 14 , wherein said DNA comprises an MHC class I gene.  
     
     
         18 . The method of  claim 14 , wherein said DNA comprises an MHC class II gene.  
     
     
         19 . The method of  claim 14 , wherein said DNA is inserted into said cell by transduction.  
     
     
         20 . The method of  claim 19 , wherein said DNA is inserted into said cell by a retrovirus.  
     
     
         21 . The method of claim  20 , wherein said retrovirus is a Moloney-based retrovirus.