Methods of modulating T cell or natural killer cell activity with anti-P-selectin glycoprotein ligand 1 antibodies
Compounds that bind to P-Selectin Glycoprotein 1 (PSGL-1) on the surface of T cells or natural killer (NK) cells can be used to induce T cell or NK cell depletion and/or to induce T cell or NK cell apoptosis. The compounds and methods of the invention can be used to control unwanted T cell- or NK cell-mediated immune responses in conditions such as autoimmune diseases, transplant rejection, and allergic diseases.
1. A method of reducing an excessive or unwanted T cell-mediated immune response in an individual diagnosed as having a condition characterized by an excessive or unwanted T cell-mediated immune response, the method comprising:
selecting an anti-PSGL-1 antibody based on its ability both to bind specifically to P-Selectin Glycoprotein Ligand-1 (PSGL-1) on the surface of an activated T cell and to induce apoptosis of the activated T cell; and
administering to the individual a composition comprising an effective amount of the selected apoptosis-inducing anti-PSGL-1 antibody to reduce the excessive or unwanted T cell-mediated immune response in the individual.
2. The method of claim 1 , wherein the antibody is a monoclonal antibody.
3. The method of claim 2 , further comprising administering to the individual an antibody that binds to the monoclonal antibody and induces cross-linking of a plurality of PSGL-1 antigens on the surface of the T cell.
4. The method of claim 1 , wherein the condition characterized by an excessive or unwanted T cell-mediated immune response is an autoimmune disease.
5. The method of claim 1 , wherein the condition characterized by an excessive or unwanted T cell-mediated immune response if rejection of an allogeneic or xenogeneic transplant.
6. The method of claim 1 , wherein the condition characterized by an excessive or unwanted T cell-mediated immune response is an allergic disease.
7. The method of claim 1 , wherein the condition characterized by an excessive or unwanted T cell-mediated immune response is a T cell cancer.
8. The method of claim 1 , wherein the activated T cell is a CD4 + T cell.
9. The method of claim 1 , wherein the activated T cell is a CD8 + T cell.
10. The method of claim 1 , further comprising:
detecting a number of T cells in a first biological sample taken from the individual before the administration of the composition; and
comparing the number of T cells detected in the first biological sample with a number of T cells in a second biological sample taken from the individual after the administration of the composition.
11. A method of inducing the death of an activated T cell or a natural killer (NK) cell, the method comprising:
selecting an anti-PSGL-1 antibody based on its ability both to bind specifically to P-Selectin Glycoprotein Ligand-1 (PSGL-1) on the surface of an activated T cell and to induce apoptosis of the activated T cell;
providing an activated T cell or NK cell expressing PSGL-1 on its cell surface; and
contacting the activated T cell or NK cell with an effective amount of the selected apoptosis-inducing anti-PSGL-1 antibody to induce apoptosis of the activated T cell or NK cell.
12. The method of claim 11 , wherein the antibody is a monoclonal antibody.
13. The method of claim 12 , further comprising contacting the monoclonal antibody with an antibody that binds to the monoclonal antibody and induces cross-linking of a plurality of PSGL-1 antigens on the surface of the activated T cell or NK cell.
14. The method of claim 11 , wherein the activated T cell or NK cell is an activated T cell.
15. The method of claim 11 , wherein the activated T cell or NK cell is a CD4 + T cell.
16. The method of claim 11 , wherein the activated T cell or NK cell is a CD8 + T cell.
17. The method of claim 11 , further comprising assessing viability of the activated T cell or NK cell after the contacting with the antibody.
18. The method of claim 11 , wherein the activated T cell or NK cell is an NK cell.