Regulatory t cell mediator proteins and uses thereof

Abstract

The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates αCD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon αCD3/αGITR stimulation. This protein has been designated Treg-sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed.

1 - 6 . (canceled) 
     
     
         7 . An isolated or recombinant human cell which has been engineered to express a human PD-L3 polypeptide or fragment, wherein said PD-L3 polypeptide or fragment promotes T cell proliferation and T cell activity. 
     
     
         8 . The human cell of  claim 7  which comprises a T cell. 
     
     
         9 . The T cell of  claim 8  which comprises a Treg cell. 
     
     
         10 . A method of promoting T cell activity in a subject in need thereof comprising
 (i) isolating a cell from a human donor;   (ii) engineering said isolated cell such that it expresses human PD-L3 polypeptide or fragment, wherein said PD-L3 polypeptide or fragment promotes T cell proliferation and T cell activity and   (iii) introducing said engineered human cell into a human recipient who comprises a condition wherein increased T cell proliferation and activity is desired.   
     
     
         11 . The method of  claim 10  wherein the human recipient and/or human donor comprise cancer or an infectious condition. 
     
     
         12 . The method of  claim 10  wherein the human recipient and the human donor are the same. 
     
     
         13 . The method of  claim 10  wherein the isolated cell is a T cell. 
     
     
         14 . The method of  claim 10  wherein the isolated cell is a Treg cell. 
     
     
         15 . A method of promoting T cell activity in a subject in need thereof comprising
 (i) isolating one or more immune cells from a human donor;   (ii) contacting said isolated one or more immune cells with a human PD-L3 polypeptide or fragment, wherein said PD-L3 polypeptide or fragment promotes T cell proliferation and T cell activity and   (iii) introducing said human cells with have been contacted according to (ii) into a human recipient who comprises a condition wherein increased T cell proliferation and activity is desired.   
     
     
         16 . The method of  claim 15  wherein the human recipient comprises cancer or an infectious condition. 
     
     
         17 . The method of  claim 15  wherein the human recipient and the human donor are the same. 
     
     
         18 . The method of  claim 15  wherein the isolated immune cells comprise T cells. 
     
     
         19 . The method of  claim 10  wherein the isolated immune cells comprise Treg cells.