Method to Prevent Graft Rejection Using TGF-Beta to Induce T Suppressor Cells

Abstract

The invention relates to compositions and methods useful for preventing graft rejection in a recipient following organ transplantation.

1 . One or more suppressor T cells capable of decreasing graft rejection of a solid organ by a recipient made by the process comprising:
 a) isolating peripheral blood mononuclear cells (PBMC) from a recipient and an organ donor;   b) irradiating T cell-depleted mononuclear cells from said organ donor PBMC; and   c) combining ex vivo said recipient PBMC with said donor irradiated T cell-depleted mononuclear cells and a regulatory composition comprising TGF-β to induce one or more recipient suppressor T cells.   
   
   
       2 . A population of suppressor T cells capable of decreasing graft rejection of a solid organ by a recipient made by the process comprising:
 a) isolating peripheral blood mononuclear cells (PBMC) from a recipient and an organ donor;   b) irradiating T cell-depleted mononuclear cells from said organ donor PBMC;   c) combining ex vivo said recipient PBMC with said donor irradiated T cell-depleted mononuclear cells and a regulatory composition comprising TGF-β to induce a PBMC population comprising one or more recipient suppressor T cells; and   d) wherein a recipient suppressor T cell population is produced by expanding said recipient suppressor T cells.   
   
   
       3 . The suppressor T cells according to  claim 1  or  2 , wherein said regulatory composition further comprises cytokines selected from the group consisting of IL-2 and IL-15. 
   
   
       4 . The suppressor T cells according to  claim 1  or  2 , wherein said PBMC from said recipient are enriched for CD4+ T cells. 
   
   
       5 . The suppressor T cells according to  claim 4 , wherein said CD4+ cells are enriched for naive CD4+ T cells. 
   
   
       6 . The suppressor T cells according to  claim 1  or  2 , wherein said PBMC from said recipient are enriched for CD8+ T cells.