The use of KIM-1 antagonists to inhibit signaling between a T cell and a second cell, e.g., an antigen-presenting cell, is disclosed. Such inhibition is useful for treatment of diseases including various autoimmune diseases and graft-versus-host disease. Also disclosed is the use of a KIM-1 antagonist to inhibit secretion of IFN-.gamma. by lymphocytes or other immune cells in a mammal. Inhibition of IFN-.gamma. is useful for treatment of inflammatory diseases or disorders, e.g., inflammatory bowel disease.