Complete human monoclonal IgG4lambda specific for CTLA-4 and uses thereof for detection of soluble CTLA-4 and isolation of regulatory cells

Abstract

The present invention provides a CTLA-4 non-blocking agent of a complete human antibody nature, thus is non-immunogenic in a human. The immunoassay method using such a non-blocking agent measures the CTLA-4 content in a sample of a human subject. The present invention further provides a novel method for isolating human regulatory T cells. The resultant enriched and depleted cellular populations are useful in treating or ameliorating of human diseases.

1 . A method of isolating regulatory T cells from human samples, said method comprising:
 (a) contacting a population of suspended cells in a sample with a CTLA-4 non-blocking agent that recognizes the extracellular domain of CTLA-4, wherein said CTLA-4 non-blocking agent is non-immunogenic in a human and comprises an antibody or an antigen-binding fragment thereof; and   (b) selecting cells that bind to the CTLA-4 non-blocking agent, wherein the selected cells are enriched for regulatory T cells, and   (c) further comprising transfusing the enriched population of said regulatory T cells into a subject to suppress the autoimmune response.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1  wherein the isolated and enriched cellular population is expanded in cell culture before transfusing into a subject. 
     
     
         4 . The method of  claim 1  wherein the negative or exclusive cellular populations of step (b) that do not bind to the CTLA-4 non-blocking agent are deficient in regulatory T cells. 
     
     
         5 . The method of  claim 4  further comprising introducing said depleted cellular population into a subject to enhance the activation of T cells. 
     
     
         6 . The method of  claim 5  wherein the depleted cellular population further contacts an antigen in cell culture before introducing into a subject.