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[摘要]：Large granular lymphocyte (LGL) leukemia is a clonal lymphoproliferative disease of mature T and natural killer cells. The etiology of LGL leukemia is unknown. IL-15 is an inflammatory cytokine that stimulates T and natural killer cells and is critical for their survival and proliferation. IL-15 signals through a heterotrimeric receptor that is composed of a private receptor, IL-15R alpha and IL-2/IL-15R beta and gamma(c) shared with IL-2. Using a newly developed assay, we demonstrated increased levels of soluble IL-15R alpha in the serum of patients with T-LGL leukemia. Furthermore, IL-15R alpha mRNA levels were also up-regulated in the PBMCs of these patients. FACS analysis indicated that IL-15R alpha was expressed both on monocytes as well as on some CD8(+) leukemic cells of the patients. Interestingly, the mRNA levels of IFN-gamma, a known inducer of IL-15R alpha, were also up-regulated in patients' PBMCs. Moreover, PBMCs of some T-LGL patients proliferated at higher levels in response to exogenously added IL-15 compared with those of normal donors. In summary, our study demonstrated increased expression of IL-15R alpha in T-LGL leukemia. It is conceivable that higher IL-15R alpha expression may lower IL-15 response threshold in vivo and, therefore, may contribute to the pathogenesis of the disease. (Blood. 2012; 119(1): 137-143) |
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