Regulatory T cell mediator proteins and uses thereof
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 T reg -sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed.
1. A method of promoting T cell immunity against a viral infectious agent comprising administering an effective amount of an anti-PD-L3 antibody or antibody fragment that specifically binds to the extracellular region of the human PD-L3 protein having the sequence in SEQ ID NO:4, wherein said anti-PD-L3 antibody or antibody fragment antagonizes the immunosuppressive effect of PD-L3 on T cell immunity in vivo, and thereby potentiates T cell immune response against the viral infectious agent.
2. The method of claim 1 , wherein the anti-PD-L3 antibody or antibody fragment antagonizes one or more of the following effects of PD-L3 on T cell function in vivo:
(1) suppression of T cell activation or differentiation;
(2) suppression of CD4+T cell proliferation,
(3) suppression of CD8+T cell proliferation and
(4) suppression of cytokine production by T cells.
3. The method of claim 1 , wherein the antibody or antibody fragment is a chimeric, human or humanized antibody or fragment thereof.
4. The method of claim 1 , wherein the antibody fragment is selected from a Fab, F(ab′)2, Fv, Fd, and a scFv.
5. The method of claim 1 , wherein the antibody is an IgG1.
6. The method of claim 1 , which promotes T cell-mediated killing of virally infected cells.