Therapeutic uses for MDC and MDC antagonists

Abstract

The present invention provides purified and isolated polynucleotide sequences encoding a novel human macrophage-derived C—C chemokine designated Macrophage Derived Chemokine (MDC), and polypeptide analogs thereof. Also provided are materials and methods for the recombinant production of the chemokine, and purified and isolated chemokine protein, and polypeptide analogs thereof. Also provided are antibodies reactive with the chemokine and methods of making and using all of the foregoing.

1 - 18 . (canceled)  
     
     
         19 . A method of modulating chemotaxis of C—C chemokine receptor-four positive (CCR4 + ) systemic memory T cells in a mammalian host, the method comprising: 
 administering a CCR4 modulating agent to a mammalian host in an amount effective to modulate chemotaxis of said cells.    
     
     
         20 . The method of  claim 19 , wherein said systemic memory T cells are further characterized as CD4 + /CD45RA − /CD45RO + .  
     
     
         21 . The method of  claim 19 , wherein said CCR4 +  modulating agent comprises a Macrophage Derived Chemokine (MDC) polypeptide that comprises the amino acid sequence of residues 1-69 of SEQ ID NO: 2.  
     
     
         22 . The method of  claim 19 , wherein the CCR4 +  modulating agent comprises a polypeptide that comprises an amino acid sequence that is encoded by a polynucleotide that hybridizes to a DNA comprising the non-coding strand complementary to nucleotides 92 to 298 of SEQ ID NO: 1, under the following stringent hybridization conditions: hybridization at 42° C. in a hybridization solution comprising 5×SSC, 20 mM NaPO4, pH 6.8, 50% formamide; and washing at 42° C. in a wash solution comprising 0.2×SSC; 
 wherein the polypeptide binds CCR4 + .    
     
     
         23 . The method of  claim 19 , wherein said CCR4 +  modulating agent is a MDC antibody.  
     
     
         24 . The method of  claim 23 , wherein said antibody is a monoclonal antibody.  
     
     
         25 . The method of  claim 24 , wherein said antibody is selected from the group consisting of: 252Y, 252Z, and 272D.  
     
     
         26 . The method of  claim 19 , wherein said CCR4 +  modulating agent is Thymus and Activation-Regulated Chemokine (TARC).  
     
     
         27 . A method of inhibiting inflammation comprising: 
 administering a composition comprising a CCR4 modulating agent that interferes with MDC-induced chemotaxis of CCR4 +  systemic memory T cells to a mammalian host in an amount effective to modulate MDC-induced chemotaxis of CCR4 +  systemic memory T cells.