Generation of antigen specific T suppressor cells for treatment of rejection

Abstract

This invention provides a method of generating antigen specific allospecific human-suppressor CD8+CD28− T cells. This invention also provides a method of generating xenospecific human suppressor CD8+CD28− T cells. This invention further provides a method of generating allopeptide antigen specific human suppressor CD8+CD28− T cells. Methods of treatment for, reduction of risk of rejection of allografts and xenografts and autoimmune diseases using the human suppressor CD8+CD28− T cells so produced are also provides, as are methods of preventing rejection and autoimmune diseases, and vaccines comprising the produced suppressor T cells. Methods of diagnosis to determine whether a level of immuno-suppressant therapy requires a reduction are provided.

1 - 55 . (canceled)  
     
     
         56 . A method of inducing tolerance to a xenograft tissue or organ in a subject which comprises administering to the subject tolerogenic antigen presenting cells (APC) which overexpress monocyte inhibitory receptor (MIR), thereby inducing tolerance to the xenograft in the subject.  
     
     
         57 . An antigen presenting cell (APC) which overexpresses ILT3, wherein the APC comprises a retroviral vector comprising a nucleic acid sequence which encodes ILT3 and overexpresses ILT3.  
     
     
         58 . The APC of  claim 57 , wherein the APC is an APC from a subject who is a tissue or organ transplant donor.  
     
     
         59 . A method of inducing tolerance to a xenograft tissue or organ transplant in a subject which comprises: 
 (a) introducing to an antigen presenting cell (APC) of a tissue or organ transplant donor a vector which overexpresses ILT3, wherein the vector comprises a nucleic acid sequence which encodes ILT3 and overexpresses ILT3; and    (b) administering the APC of step (a) to the subject, thereby inducing tolerance to the xenograft in the subject.    
     
     
         60 . The method of  claim 59 , wherein the vector is a retroviral vector.  
     
     
         61 . A method of inducing tolerance to an allograft tissue or organ in a subject which comprises: 
 (a) introducing to an antigen presenting cell (APC) of a tissue or organ transplant donor a vector which overexpresses ILT3, wherein the vector comprises a nucleic acid sequence which encodes ILT3 and overexpresses ILT3; and    (b) administering the APC of step (a) to the subject, thereby inducing tolerance to the allograft in the subject.    
     
     
         62 . The method of  claim 61 , wherein the vector is a retroviral vector.  
     
     
         63 . A method of treating an autoimmune disease in a subject which comprises: 
 (a) introducing to an antigen presenting cell (APC) of a subject having the autoimmune disease a vector which overexpresses ILT3, wherein the vector comprises a nucleic acid sequence which encodes ILT3 and overexpresses ILT3;    (b) administering the APC of step (a) to the subject, thereby treating the autoimmune disease in the subject.    
     
     
         64 . The method of  claim 63 , wherein the vector is a retroviral vector.  
     
     
         65 . The method of  claim 63 , wherein the autoimmune disease is selected from the group consisting of diabetes, rheumatoid arthritis, and multiple sclerosis.  
     
     
         66 . A method of determining the appearance of T suppressor (Ts) cells which comprises detecting the level of expression of ILT3, ILT4, and ILT2 protein in APCs of a subject, wherein the subject is a xenograft tissue or organ transplant recipient which comprises: 
 (a) obtaining a sample from the subject; and    (b) detecting in the sample of step (a) overexpression of mRNA which encodes the ILT3, ILT4, and ILT2 protein in the APC of the subject, wherein detection of overexpression of mRNA which encodes the ILT3, ILT4, and ILT2 protein indicates the appearance of T suppressor cells in the subject.    
     
     
         67 . The method of  claim 66 , wherein the Ts are xenospecific human suppressor CD8+CD28− T cells.  
     
     
         68 . A method of determining the appearance of T suppressor (Ts) cells which comprises detecting the level of expression of ILT3, ILT4, and ILT2 protein in APCs of a subject, wherein the subject is an allograft tissue or organ transplant recipient which comprises: 
 (a) obtaining a sample from the subject; and    (b) detecting in the sample of step (a) overexpression of mRNA which encodes the ILT3, ILT4, and ILT2 protein in the APC of the subject, wherein detection of overexpression of mRNA which encodes the ILT3, ILT4, and ILT2 protein indicates the appearance of T suppressor cells in the subject.    
     
     
         69 . The method of  claim 68 , wherein the Ts are allospecific human suppressor CD8+CD28− T cells.