Methods for inducing antigen-specific T cell tolerance

Abstract

Methods for inducing antigen-specific T cell tolerance are disclosed. The methods involve contacting a T cell with: 1) a cell which presents antigen to the T cell, wherein a ligand on the cell interacts with a receptor on the surface of the T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor on the surface of the T cell which inhibits interaction of the ligand on the antigen presenting cell with the receptor on the T cell. In a preferred embodiment, the cell which presents antigen to the T cell is a B cell and the receptor on the surface of the T cell which mediates contact-dependent helper effector function is gp39. Preferably, the antagonist is an anti-gp39 antibody or a soluble gp39 ligand (e.g., soluble CD40). The methods of the invention can be used to induce T cell tolerance to a soluble antigen or to an allogeneic cell. The methods of the invention can also be used to induce tolerance in cases of bone marrow transplantation and other organ transplants and to inhibit graft-versus-host disease.

1 . A method for reducing T cell responsiveness in vivo to an autoantigen expressing cell, which method comprises administering to a subject in need of such treatment: 
 (a) an antigen-presenting cell that presents an autoantigen;    (b) an anti-gp39 antibody or anti-gp39 fragment which binds to an antigen, which antigen is bound by MR1 which is a monoclonal antibody produced by a hybridoma having ATCC Accession No. HB 11048; and    wherein the anti-gp39 antibody or anti-gp39 fragment is administered prior to, concurrent with, or subsequent to administration of the antigen-presenting cell in an amount effective to reduce T cell responsiveness to the antigen-presenting cell.    
   
   
       2 . The method of  claim 1 , wherein the antigen-presenting cell is selected from the group consisting of B lymphocytes, monocytes, dendritic cells, Langerhans cells, keratinocytes, endothelial cells, astrocytes, fibroblasts and oligodendrocytes.  
   
   
       3 . The method of  claim 1 , wherein the antigen-presenting cell is a lymphoid cell.  
   
   
       4 . The method of  claim 1 , wherein the antigen-presenting cell is a B lymphocyte.  
   
   
       5 . The method of  claim 4 , wherein the B lymphocyte is an activated B lymphocyte.  
   
   
       6 . The method of  claim 5 , wherein the activated B lymphocyte is a splenic activated B lymphocyte.  
   
   
       7 . The method of  claim 1 , wherein the antigen-presenting cell is a peripheral blood lymphocyte.  
   
   
       8 . The method of  claim 1 , wherein the antigen-presenting cell is a dendritic cell.  
   
   
       9 . The method of  claim 1 , wherein the antigen-presenting cell is a Langerhans cell.  
   
   
       10 . The method of  claim 1 , wherein the antigen-presenting cell is a bone marrow activated lymphocyte.  
   
   
       11 . The method of  claim 1 , wherein the anti-gp39 antibody is an anti-human anti-gp39 antibody.  
   
   
       12 . The method of  claim 11 , wherein the anti-human anti-gp39 antibody is humanized.  
   
   
       13 . The method of  claim 11 , wherein the anti-human anti-gp39 antibody is a chimeric anti-human anti-gp39 antibody containing human constant regions.  
   
   
       14 . The method of  claim 1 , wherein the anti-gp39 antibody fragment is selected from the group consisting of a Fab fragment, a F(ab′) 2  fragment, a VH region, and an FV region.