The human interleukin-2 receptor is being studied to understand specific critical components of the T cell immune response in normal and neoplastic cells. When T-cells are activated by antigen or mitogen lectin, both IL-2 and IL-2 receptor expression are induced. IL-2 and IL-2 receptors control the magnitude and duration of the T-cell immune response based on the amount of IL-2 produced, the levels of receptors expressed, and the time course of each of these events. Whereas low levels of intermediate affinity IL-2 receptors are expressed on resting cells, following antigen stimulation, expression of both high and low affinity IL-2 receptors is potently induced. Three chains of the IL-2 receptor are now known to exist, namely IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma. IL-2Ralpha and IL- 2beta have been cloned. Dr. Leonard cloned IL-2Ralpha as a post-doctoral fellow, and the current lab discovered IL-2Rbeta. In the past year, major advances have been made in a number of areas. Significant progress has been in studies utilizing the expression of the IL-2alpha and beta chain cDNAs in 32D cells to elucidate features of IL-2 mediated signal transduction. It was shown that IL-2 can induce signals overlapping but distinct from IL-3 in IL-2Rbeta transfected 32D cells to elucidate features of IL-2 mediated signal transduction. It was shown that IL-2 can induce signals overlapping but distinct from IL-3 in IL-2Rbeta transfected 32D cells capable of responding to both growth factors. Although tyrosine kinases are critically involved based on experiments using tyrosine kinase inhibitors, it is clear that the previously reported p56lck tyrosine kinase is not obligately required in all cells in order to transduce an IL-2 mediated signal. Further, it was discovered that tyrosine kinases may be involved in apoptosis (programmed cell death). Multiply IL-2Rbeta mutants for use in signaling studies have been prepared. It has also been demonstrated for the first time that human neutrophils express IL-2 receptors and respond to IL-2. Their response allows cytotoxicity towards tumor targets and the killing of Candida albicans, a human pathogen. Thus, progress has been made in elucidating both the mechanism of IL-2 signaling and in identifying a completely new physiological role for IL-2, a feature that could have important implications in IL-2 based immunotherapy.
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