The present invention is based, in part, on expression studies of IL-2 and IL-15 receptor subunits by cycling T cells in vivo. In one embodiment, theinvention generally features novel combinations of IL-2 and IL-15 antagonistsand methods of suppressing the immune response by administering theseantagonists. In each case, suppression is achieved by administration of afirst agent that targets an IL-15 molecule or an IL-15 receptor (IL-15R) and asecond agent that targets an IL-2 molecule or an IL-2 receptor (IL-2R). Moregenerally, the invention features novel combinations of agents that, whenadministered to a patient (or to a transplant ex vivo, reduce the number ofantigen-reactive T cells. For example, the invention features compositions(e.g., pharamaceutically acceptable compositions) that include two or moreagents, each of which promote T cell death. Alternatively, the composition cancontain at least one agent that promotes T cell death and at least one agentthat inhibits T cell proliferation. The agent that promotes T cell death canpromote AICD (activation induced cell death), passive cell death, ADCC(antibody dependent cell-mediated cytotoxicity) or CDC (complement directedcytotoxicity).
