Immunomodulation by interleukin-2 receptor targeted therapy.

The interleukin-2 receptor (IL-2R) is expressed on proliferating T-lymphocytes following antigen stimulation. Activated IL-2R bearing lymphocytes accumulate as cellular infiltrates in autoimmune thyroiditis, insulin-dependent diabetes mellitus, rheumatoid arthritis and graft rejection. Affected cells in Hodgkin's disease, hairy cell leukaemia, non-Hodgkin's lymphoma, cutaneous T-cell lymphoma and lymphoid blast crises of chronic myeloid leukaemia also express IL-2R. Anti-IL-2R monoclonal antibodies or chimeric IL-2R toxins provide a way of selective elimination of such cells. These have been used in experimental models of autoimmunity and transplantation with beneficial results, providing a novel way of selective immunosuppression. In open uncontrolled trials, chimeric IL-2R toxin was found to be safe and effective in patients with refractory rheumatoid arthritis, insulin-dependent diabetes mellitus and IL-2R bearing leukaemias and lymphomas.