Human CD8+ T cells store RANTES in a unique secretory compartment and release it rapidly after TcR stimulation

Human CD8+ T cells store RANTES in a unique secretory compartment and release it rapidly after TcR stimulation
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DOI:
10.1016/s1074-7613(04)00027-5
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发表时间:
2004-02-01
期刊:
影响因子:
32.4
通讯作者:
Henkart, PA
Henkart, PA
中科院分区:
医学1区
文献类型:
--
作者:
Catalfamo, M;Karpova, T;Henkart, PA

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趋化因子RANTES在人CD 8(+)T细胞活化后迅速分泌,在第一个小时内出现环己酰亚胺耐药爆发。在来自血液的纯化记忆和效应表型CD 8+细胞以及原始细胞中观察到这种模式。相反,这些细胞分泌的其他趋化因子和干扰素-γ对放线菌酮敏感,仅在滞后后才能检测到。CD 8(+)记忆细胞和效应细胞以及原始细胞的免疫荧光显微镜显示RANTES存在于细胞内囊泡中,不与细胞毒性颗粒标志物或其他确定的细胞质区室标志物显著共定位。免疫电子显微镜证实,RANTES是存储在小泡不同的溶酶体分泌颗粒。RANTES(+)囊泡响应于TcR接合而快速增殖,并且更快地从细胞质中耗尽。这些结果表明,CD 8 + T细胞具有两个不同的TcR调节的分泌区室,其特征在于不同的动员动力学,效应分子和生物学功能。
The chemokine RANTES is secreted rapidly after activation of human CD8(+) T cells, with a cycloheximide-resistant burst during the first hour. This pattern was observed in purified memory and effector phenotype CD8+ cells from blood as well as in blasts. In contrast, secretion of other chemokines and interferon-gamma by these cells was sensitive to cycloheximide and detectable only after a lag. Immunofluorescence microscopy of CD8(+) memory and effector cells and blasts showed RANTES present in intracellular vesicles that do not significantly colocalize with cytotoxic granule markers or other markers of defined cytoplasmic compartments. Immunoelectron microscopy confirmed that RANTES is stored in small vesicles distinct from the lysosomal secretory granules. RANTES(+) vesicles polarize rapidly in response to TcR engagement and are more rapidly depleted from the cytoplasm. These results show that CD8+ T cells have two distinct TcRregulated secretory compartments characterized by different mobilization kinetics, effector molecules, and biological function.