Costimulatory blockade and mixed chimerism in allotransplantation

Abstract

Use of the blockade of costimulation and hematopoietic stem cells in allograft transplantation.

What is claimed is:  
     
         1 . A method of promoting acceptance, by a recipient mammal, of a graft from a donor mammal of the same species comprising: 
 administering to the recipient, an inhibitor of the CD40 ligand-CD40 costimulatory interaction;    introducing into the recipient mammal, hematopoietic stem cells, and    implanting the graft in the recipient.    
     
     
         2 . The method of  claim 1 , further comprising administering an inhibitor of the CD28-B7.  
     
     
         3 . The method of  claim 1 , wherein the CD40 ligand-CD40 interaction is inhibited by administering an antibody or soluble ligand or receptor for the CD40 ligand or CD40.  
     
     
         4 . The method of  claim 1 , wherein an anti-CD40L antibody is administered.  
     
     
         5 . The method of  claim 2 , wherein the CD28-B7 interaction is inhibited by administering a soluble ligand or receptor or antibody for the CD28 or B7.  
     
     
         6 . The method of  claim 5 , wherein CTLA4/Ig is administered.  
     
     
         7 . The method of  claim 2 , wherein CTLA4-Ig and an anti-CD40L antibody are administered.  
     
     
         8 . The method of  claim 2 , wherein a blocker of the CD40/CD40L interaction is administered prior to administration of a blocker of the CD28/B7 interaction.  
     
     
         9 . The method of  claim 1 , wherein the recipient mammal is a human.  
     
     
         10 . The method of  claim 1 , wherein the method is practiced without thymic irradiation or anti-T cell antibodies.  
     
     
         11 . The method of  claim 1 , wherein the method is practiced without T cell depletion or inactivation.  
     
     
         12 . The method of  claim 1 , wherein the method is practiced with T cell depletion or inactivation.  
     
     
         13 . The method of  claim 1 , wherein the method is practiced with partial T cell depletion or inactivation.