Allogeneic and xenogeneic transplantation

Abstract

The invention provides methods for restoring or inducing imnmunocompetence, the methods including the step of introducing donor thymic tissue into the recipient. The invention also provides methods for inducing tolerance in a recipient including introducing donor thymic tissue into the recipient. The invention further provides methods of inducing tolerance including administering to the recipient a short course of help reducing treatment or administering a short course and methods of prolonging the acceptance of a graft by administering a short course of an immunosuppressant.

1 . A method of restoring or promoting the thymus-dependent ability for T cell progenitors to develop into mature functional T cells in a primate recipient which is capable of producing T cell progenitors but which is thymus-function deficient, the method comprising introducing into said primate recipient xenogeneic fetal or neonatal thymus tissue from a donor animal of a different species, so that recipient T cells can mature in said implanted donor thymus tissue.  
     
     
         2 . The method of  claim 1 , wherein the donor animal is a swine.  
     
     
         3 . The method of  claim 2 , further comprising implanting swine fetal liver tissue in said recipient.  
     
     
         4 . The method of  claim 2 , wherein said primate recipient is a human.  
     
     
         5 . The method of  claim 2 , wherein said donor swine is a miniature swine.  
     
     
         6 . The method of  claim 2 , wherein said swine thymus tissue is capable of supporting in the recipient primate clonal deletion or anergy of thymocytes reactive with donor xenoantigens.  
     
     
         7 . The method of  claim 2 , further comprising introducing swine hematopoietic cells into said recipient and inactivating NK cells of said recipient.  
     
     
         8 . The method of  claim 2 , further comprising the step of inactivating mature CD4 +  T cells in the recipient.  
     
     
         9 . A method of inducing tolerance in a recipient primate of a first species to a graft obtained from a donor animal of a second discordant species, said method comprising 
 prior or simultaneous with transplantation of said graft, introducing into said recipient, thymic tissue from the second species; and    implanting said graft in said recipient.    
     
     
         10 . The method of  claim 9 , wherein the donor animal is a swine.  
     
     
         11 . The method of  claim 10 , wherein the same swine is the donor of both the graft and the thymic tissue.  
     
     
         12 . The method of  claim 9 , wherein said primate is a human.  
     
     
         13 . The method of  claim 9 , said method further comprising the step of, prior or simultaneous with transplantation of said graft, inactivating mature CD4 +  T cells of the recipient.  
     
     
         14 . The method of  claim 9 , further comprising the step of, prior to thymic tissue transplantation, irradiating the recipient with low dose whole body irradiation.  
     
     
         15 . The method of  claim 14 , wherein said low dose irradiation is at least 100 rads and less than 400 rads.  
     
     
         16 . The method of  claim 9 , further comprising the step, prior to thymic tissue transplantation, adsorbing natural antibodies from the blood of said recipient.  
     
     
         17 . The method of  claim 9 , wherein said thymic tissue is capable of supporting, in the recipient primate, clonal deletion or anergy of thymocytes reactive with donor xenoantigens.  
     
     
         18 . The method of  claim 9 , wherein hematopoietic cells are administered to said recipient and wherein the method includes inactivating NK cells of said recipient.  
     
     
         19 . The method of  claim 9 , wherein said primate recipient is a human and said donor is a miniature swine.  
     
     
         20 . A method of providing mature recipient T cells in a primate recipient which is thymus function deficient, comprising introducing into the primate recipient swine xenogeneic donor thymic tissue, so that recipient T cells can mature in said implanted swine donor thymic tissue.  
     
     
         21 . The method of  claim 20 , wherein said primate is a human and said donor is a miniature swine.  
     
     
         22 . The method of  claim 20 , wherein said thymus function is deficient in said recipient due to an immune disorder.  
     
     
         23 .- 39 . (canceled)