Immune Regulation

Abstract

A method of regulating the immune system of a subject that involves removing antigen presenting cells from subject and loading preselected class II peptide fragments onto the subjects APC's outside the body of the subject.

1 . A method of inhibiting allograft rejection in a subject in need thereof, the method comprising:
 (a) loading a peptide fragment of an α or β chain of a preselected major histocompatibility complex (MHC) class II protein from the subject onto antigen presenting cells (APCs) in the subject, wherein the loading comprises administering to the subject (i) an expression vector encoding one or both of the α or β chain of the preselected MHC class II protein or (ii) a purified form of the peptide fragment,   wherein the purified form of the peptide fragment or the expression vector are administered in an amount sufficient to activate autogenous peripheral T regulatory cells and suppress alloreactive autogenous cytotoxic T cells in the subject, thereby inhibiting allograft rejection in the subject.   
     
     
         2 . The method of  claim 1 , comprising, after (a) evaluating the extent to which the subject's APCs are loaded with the peptide fragment. 
     
     
         3 - 7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the subject is human. 
     
     
         9 - 14 . (canceled) 
     
     
         15 . The method of claim  12 , wherein the activated autogenous peripheral T regulatory cells include CD4 + CD25 +  cells. 
     
     
         16 - 32 . (canceled) 
     
     
         33 . The method of  claim 1 , wherein the purified form of the peptide fragment is administered to the subject intravenously. 
     
     
         34 . The method of  claim 1 , wherein the loaded APCs are dendritic cells. 
     
     
         35 . The method of  claim 34 , wherein the dendritic cells are immature dendritic cells. 
     
     
         36 . The method of  claim 34 , wherein the dendritic cells are immature dendritic cells derived from bone marrow. 
     
     
         37 . The method of  claim 1 , wherein the expression vector encodes the a chain of the preselected MHC class II protein from the subject. 
     
     
         38 . The method of  claim 1 , wherein the expression vector encodes the f3 chain of the preselected MHC class II protein from the subject. 
     
     
         39 . The method of  claim 1 , wherein the expression vector encodes the a and chains of the preselected MHC class II protein from the subject. 
     
     
         40 . The method of  claim 1 , wherein the loading in (a) is performed prior to allograft implantation into the subject. 
     
     
         41 . The method of  claim 1 , wherein the loading in (a) is performed at the time of allograft implantation into the subject. 
     
     
         42 . The method of  claim 1 , wherein the loading in (a) is performed after allograft implantation. 
     
     
         43 . The method of  claim 42 , wherein the loading in (a) is performed at a single time point. 
     
     
         44 . The method of  claim 43 , wherein the single time point is at least two days after the allograft implantation. 
     
     
         45 . The method of  claim 43 , wherein the single time point is at least one week after the allograft implantation. 
     
     
         46 . The method of  claim 43 , wherein the single time point is at least one month after the allograft implantation. 
     
     
         47 . The method of  claim 43 , wherein the single time point is at least six months after the allograft implantation. 
     
     
         48 . The method of  claim 1 , wherein the loading in (a) is performed when the subject begins to show signs of graft rejection. 
     
     
         49 . The method of  claim 48 , wherein the signs of graft rejection are selected from the group consisting of: a decline in the function of a grafted organ, change in the subject's donor-specific antibody response, and a change in the subject's lymphocyte response to donor antigen. 
     
     
         50 . The method of  claim 1 , wherein the allograft is an organ. 
     
     
         51 . The method of  claim 50 , wherein the organ is a liver, kidney, heart, or lung. 
     
     
         52 . The method of  claim 1 , wherein the allograft is selected from the group consisting of: bone or skeletal matrix, skin, intestine, and endocrine gland. 
     
     
         53 . The method of  claim 1 , wherein the allograft is a musculocutaneous graft, a muscle flap, or hematopoietic cells. 
     
     
         54 . The method of  claim 1 , wherein the allograft is a vascularized graft. 
     
     
         55 . The method of  claim 1 , further comprising administering to the subject an agent selected from the group consisting of: cyclosporine, FK506, 15-deoxyspergualin, mycophenolate mofetil, and brequinar sodium. 
     
     
         56 . The method of  claim 1 , further comprising the administration of a cytokine 
     
     
         57 . The method of  claim 56 , wherein the cytokine is a stem cell factor, interleukin-3, or granulocyte-macrophage colony-stimulating factor.