Modulating Th2 cell levels via vMIP-I/CCR8 interaction

Abstract

The present invention relates to the agonist properties of vMIP-I for the chemokine receptor CCR8 as expressed on Th2 cells. Methods of modulating a physiological signal specific to Th2 cells comprising contacting these cells with vMIP-I, agonists and antagonists thereof are disclosed. Methods for treating disease using CCR8 antagonists are also provided. The modulation of the Th2 cell populations through the vMIP-I/CCR8 interaction provides a new means for diagnosing and treating specific disease states and immunologic conditions.

What is claimed is:  
     
         1 . A method of modulating a physiological signal specific to Th2 cells, comprising contacting said Th2 cells with vMIP-I or an agonist or antagonist thereof.  
     
     
         2 . The method of  claim 1 , wherein said modulating is: 
 a) blocking, and said contacting is with a VMIP-I antagonist;    b) inducing, and said contacting is with a VMIP-I signaling agonist; or    c) directing a response between a Th1 and Th2 response, and said contacting is with a vMIP-I antagonist or VMIP-I signaling agonist.    
     
     
         3 . The method of  claim 2 , wherein said antagonist is an antibody.  
     
     
         4 . The method of  claim 3 , wherein said antibody binds to a vMIP-I.  
     
     
         5 . The method of  claim 2 , wherein said modulating is directing said response to a Th2 response, and said contacting is with said vMIP-I signaling agonist.  
     
     
         6 . The method of  claim 1 , wherein said physiological signal is a proliferation, apoptotic, differentiation, or chemoattraction signal.  
     
     
         7 . The method of  claim 1 , wherein said contacting is with another chemokine or cytokine agonist or antagonist, including IL-12, IL-12 antagonist, IL-1γ, or IL-1γ antagonist.  
     
     
         8 . A method of treating an HHV-8 viral infection in a mammal comprising administering to said mammal an effective amount of a CCR8 antagonist or a vMIP-I antagonist.  
     
     
         9 . The method of  claim 8 , wherein said antagonist is an antibody.  
     
     
         10 . The method of  claim 9 , wherein said antibody binds to a CCR8 ligand or to CCR8.  
     
     
         11 . The method of  claim 10 , wherein said vMIP-I antagonist is a vMIP-I antibody.  
     
     
         12 . The method of  claim 10 , wherein said CCR8 antagonist is an I-309 antibody.  
     
     
         13 . The method of  claim 8 , wherein said treating is in combination with an effective amount of another chemokine or cytokine agonist or antagonist.  
     
     
         14 . The method of  claim 13 , wherein the chemokine or cytokine agonist or antagonist is selected from the group consisting of IL-12, IL-12 antagonist, IL-18, or IL-18 antagonist.  
     
     
         15 . A method of treating an autoimmune disease in a mammal comprising administering to said mammal an effective amount of a CCR8 antagonist or vMIP-I antagonist.  
     
     
         16 . The method of  claim 15 , wherein said antagonist is an antibody.  
     
     
         17 . The method of  claim 15 , wherein said antibody binds to a CCR8 ligand or to CCR8.  
     
     
         18 . A method of treating a bacterial or parasitic infection in a mammal comprising administering to said mammal an effective amount of a CCR8 agonist.  
     
     
         19 . The method of  claim 18 , wherein said CCR8 agonist is VMIP-I.  
     
     
         20 . The method of  claim 18 , wherein said CCR8 agonist is I-309.