METHODS FOR INDUCING T CELL NON-RESPONSIVENESS TO A TISSUE OR ORGAN GRAFT

摘要

Methods for inducing T cell tolerance to a tissue or organ graft in a transplant recipient are disclosed. The methods involve administering to a subject antagonists of the receptor which inhibit interaction of the ligand with the receptor, and CD8<+> T cell depleting agents. In a preferred embodiment, the molecules on the surface of the T cell which mediate contact-dependent helper effector function are CD154. Preferred CD154 antagonists and CD8<+> T cell depleting agents are anti-CD154 and CD8 antibodies. The CD154 antagonists and CD8<+> T cell depleting agents are typically administered to a transplant recipient following transplantation of the tissue or organ. The methods of the invention can be used to induce T cell tolerance to transplants such as pancreas, pituitary, liver, kidney, heart, lung, skin, muscle, brain tissue, nerve tissue, stomach, intestines, Adenosine Deaminase-expressing cells, and leptin-expressing cells. A method for treating a skin disorder comprising administering to a subject allogeneic or xenogeneic tissues, organs, or cells expressing donor antigens, CD154 antagonists and CD8<+> T cell depleting agents and allogeneic skin graft cells is also disclosed.