Composition and method for modulating dendritic cell-T cell interaction
The present invention relates to the use of a compound that binds to a C-type lectin on the surface of a dendritic cell, in the preparation of a composition for modulating, in particular reducing, the immune response in an animal, in particular a human or another mammal. The composition in particular modulates the interactions between a dendritic cell and a T-cell, more specifically between a C-type lectin on the surface of a dendritic cell and an ICAM receptor on the surface of a T-cell. The compositions can be used for preventing/inhibiting immune responses to specific antigens, for inducing tolerance, for immunotherapy, for immunosuppression, for the treatment of autoimmune diseases, and the treatment of allergy. The compound that binds to a C-type lectin is preferably chosen from mannose, fucose, plant lectins, antibiotics, sugars, proteins or antibodies against C-type lectins. The invention also relates to such antibodies.
1. A method for reducing a T-cell mediated immune response in an animal by inhibiting an interaction between a dendritic cell and a T cell, comprising administering to an animal in need of reducing said immune response an antibody which binds to a protein with the amino acid sequence of SEQ ID NO: 2 (DC-SIGN) on the surface of a dendritic cell, wherein said antibody reduces one or more interactions between a dendritic cell and a T cell thereby reducing said immune response in the animal, and wherein the animal is not infected with HIV.
2. The method of claim 1 wherein said animal is a mammal.
3. The method of claim 2 wherein said mammal is a human.
4. The method of claim 1 wherein said antibody reduces adhesion between DC-SIGN and an ICAM receptor on the surface of a T cell.
5. The method of claim 4 wherein said ICAM receptor is selected from the group consisting of ICAM-2 receptors and ICAM-3 receptors.
6. The method of claim 1 wherein said antibody is a monoclonal antibody.
7. The method of claim 1 wherein said antibody is selected from the group consisting of i) an antibody produced by hybridoma ECACC accession number 99040818 and ii) an antibody produced by hybridoma ECACC accession number 99040819.
8. The method of claim 1 , wherein said animal is in need of tolerance, immunotherapy or immunosuppression.
9. The method of claim 1 , wherein said animal is suffering from an autoimmune disease.
10. The method of claim 1 , wherein said animal is suffering from an allergy.
11. The method of claim 1 , wherein the antibody is administered in combination with another compound selected from the group consisting of: immunosuppressants, immunomodulants, antibiotics, auto-antigens, allergens, anti-LF3A, Tumor Necrosis Factor (TNF), anti-viral agents, and CD4 inhibitors.