Methods for inhibiting T cell responses by manipulating a common cytokine receptor gamma-chain

摘要

When stimulated through the T cell receptor(TCR)/CD3 complex without requisite costimulation through the CD28/B7 interaction, T cells enter a state of antigen specific unresponsiveness or anergy. This invention is based, at least in part, on the discovery that signaling though a common cytokine receptor &ggr; chain (e.g., interleukin-2 receptor, interleukin-4 receptor, interleukin-7 receptor, interleukin-15 receptor) prevents the induction of T cell anergy. This &ggr; chain has been found to be associated with a JAK3 kinase having a molecular weight of about 116 kD (as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis) and signaling through the &ggr; chain induces phosphorylation of the JAK3 kinase. Accordingly, methods for stimulating or inhibiting proliferation by a T cell which expresses a cytokine receptor &ggr; chain are disclosed.