Potentiation of the immune response

Abstract

A method for stimulating proliferation of T-cells containing cytoplasmic post-prolyl dipeptidase activity; the method, in one aspect, involves contacting the T-cells with an organic compound at a concentration below 10 −8 M, wherein the compound is characterized in that: (a) it is capable of crossing the membrane of T-cells to enter the cytoplasm, (b) it binds to the dipeptidase activity at a concentration of below 10 −8 M, and thus (c) stimulates proliferation of the T-cells at that concentration.

1 . A method for stimulating proliferation of T-cells of a human patient suffering from a disease state characterized by the inability of said patient's T-cells to respond normally to T-cell proliferation-inducing stimuli; said method comprising contacting said T-cells, in vitro or in vivo, with an organic compound at an in vitro concentration below 10 −8 M, or an in vivo blood concentration below 10 −8 M, wherein said compound is characterized in that it bind to the post-prolyl cleaving dipeptidase activity present in the cytoplasm of Jurkat cells.  
     
     
         2 . The method of  claim 1 , wherein said disease state is caused by HIV infection.  
     
     
         3 . The method of  claim 1 , wherein said compound is further characterized in that, at a concentration of 10 −4 M, it inhibits the cytoplasmic post-prolyl cleaving dipeptidase activity found in Jurkat T-cells.  
     
     
         4 . The method of  claim 3 , wherein said compound is further characterized in that, at a concentration of 10 −8 M, it binds to the cytoplasmic post-prolyl cleaving dipeptidase activity of CD4 +  T-cells of HIV-infected patients, to stimulate proliferation of said cells.  
     
     
         5 . The method of  claim 1 , wherein said patient is infected with HIV, and said compound is administered to said patient to bring about a blood concentration of said compound below 10 −10 M.  
     
     
         6 . The method of  claim 5 , wherein said compound is further characterized in that it is capable of crossing the membrane of human CD4 +  T-cells to enter the cytoplasm.  
     
     
         7 . A method for stimulating proliferation of T-cells which contain cytoplasmic post-prolyl cleaving dipeptidase activity and which are further characterized by the inability to respond normally to T-cell proliferation-inducing stimuli, said method comprising contacting said T-cells with an organic compound at a concentration below 10 −8 M, wherein said compound is characterized in that: 
 (a) it is capable of crossing the membrane of said T-cells to enter the cytoplasm,    (b) it binds to said dipeptidase activity at a concentration below 10- 8 M, and thus    (c) stimulates proliferation of said T-cells at said concentration.    
     
     
         8 . The method of  claim 7 , wherein said T-cells are CD4 +  cells.  
     
     
         9 . The method of  claim 8 , wherein said compound enhances the ability of said CD4 +  T-cells to proliferation in response to antigenic stimulation.  
     
     
         10 . The method of  claim 1 , wherein said compound is a serine protease inhibitor.  
     
     
         11 . The method of  claim 1 , wherein said compound is administered to an HIV-infected patient.  
     
     
         12 . The method of  claim 10 , wherein said serine protease inhibitor has a cleavage site or a binding site which mimics a post-proline serine protease cleavage site.  
     
     
         13 . (Canceled)  
     
     
         14 . (Canceled)  
     
     
         15 . (Canceled)  
     
     
         16 . (Canceled)  
     
     
         17 . A method of treating a viral infection in a patient, said method comprising administering to said patient a viral antigen, together with an adjuvant-acting amount of a compound characterized in that: 
 (a) it inhibits T-cell cytoplasmic post-prolyl dipeptidase activity at a concentration about 10- 5 M,    (b) it interacts with said dipeptidase activity at a concentration below 10 −8 M, enhancing the ability of said activity to inhibit apoptosis of T-cells of said patient, and    (c) it is capable of crossing the membrane of T-cells of said patient to enter the T-cell of cytoplasm,    wherein said compound is administered so that its concentration in the blood of said patient does not exceed 10 −8 M.    
     
     
         18 . The method of  claim 11 , wherein said virus is HIV.  
     
     
         19 . The method of  claim 17 , wherein said compound is administered orally.