Liver stromal cells for prevention and treatment of immune responses in transplantation

Abstract

The present invention encompasses methods and compositions for reducing an immune response to a transplant in a recipient by treating said recipient with an amount of liver stromal cells effective to reduce or inhibit host rejection of the transplant. Also disclosed is a method of inducing a reduced immune response against a host by foreign tissue, i.e., graft versus host disease, by treatment with liver stromal cells.

What is claimed is: 
     
         1 . A method of inhibiting an immune response in a transplant recipient comprising:
 administering to the transplant recipient, isolated adult liver stromal cells (LSCs), wherein the LSCs are incapable of differentiating into fat cells or bone producing cells, in an amount effective to inhibit an immune response by effector cells against an alloantigen to the effector cells, thereby inhibiting immune response in the transplant recipient.   
     
     
         2 . The method of  claim 1 , wherein the effector cells are T cells. 
     
     
         3 . The method of  claim 2 , wherein the T cells are from a donor and the alloantigen is from the recipient. 
     
     
         4 . The method of  claim 2 , wherein the T cells are from the recipient and the alloantigen is from a donor. 
     
     
         5 . The method of  claim 2 , wherein the T cells are present in a transplant. 
     
     
         6 . The method of  claim 1 , wherein the transplant recipient receives a bone marrow transplant, a hematopoietic stem cell transplant or a neural stem cell transplant. 
     
     
         7 . The method of  claim 1 , wherein prior to the administering liver stromal cells to a transplant recipient, the liver stromal cells have been expanded in culture. 
     
     
         8 . The method of  claim 1 , wherein the effector cells are T cells from a donor previously activated by contacting the T cells with a cell or a tissue from the recipient prior to transplantation in order to activate the T cells, and further wherein the immune response is the reactivation of the T cells. 
     
     
         9 . The method of  claim 1 , wherein the liver stromal cells are administered to the transplant recipient to treat rejection of the transplant by the recipient. 
     
     
         10 . The method of  claim 1 , wherein the effector cells are T cells from a donor previously activated by contacting the T cells with a cell or a tissue from the recipient prior to transplantation in order to activate the T cells, and further wherein the immune response is the reactivation of the T cells. 
     
     
         11 . The method of  claim 1 , wherein the liver stromal cells are human liver stromal cells. 
     
     
         12 . The method of  claim 1 , further comprising administering to the recipient an immunosuppressive agent. 
     
     
         13 . The method of  claim 1 , wherein the transplant is a solid organ selected from the group consisting of heart, pancreas, kidney, lung and liver. 
     
     
         14 . The method of  claim 1 , wherein the liver stromal cells are administered to the recipient prior to a transplant. 
     
     
         15 . The method of  claim 1 , wherein the liver stromal stem cells are administered to the recipient concurrently with a transplant. 
     
     
         16 . The method of  claim 17 , wherein the liver stromal cells are administered as part of a transplant. 
     
     
         17 . The method of  claim 1 , wherein the liver stromal cells are administered to the recipient subsequent to the transplantation of a transplant. 
     
     
         18 . The method of  claim 1 , wherein the liver stromal cells are administered intravenously to the recipient. 
     
     
         19 . The method of  claim 1 , wherein the effector cells are cells of a recipient of a donor transplant. 
     
     
         20 . The method of  claim 1 , wherein the liver stromal cells are genetically modified.