Hyaluronan binding identifies the most proliferative activated and memory T cells

Hyaluronan binding identifies the most proliferative activated and memory T cells
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DOI:
10.1002/eji.201040870
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发表时间:
2011-04-01
影响因子:
5.4
通讯作者:
Johnson, Pauline
Johnson, Pauline
中科院分区:
医学3区
文献类型:
--
作者:
Maeshima, Nina;Poon, Grace F. T.;Johnson, Pauline

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CD 44在T细胞上表达,其中其结合透明质酸的能力受到严格调节。在这里,我们研究了T细胞在免疫应答期间何时结合透明质酸。我们发现,幼稚的,鼠T细胞不结合荧光透明质酸,但诱导结合抗原诱导的T细胞活化后,在体外和体内。透明质酸结合发生在增殖的T细胞上,并且透明质酸结合细胞的百分比与活化刺激的强度相关。一小部分透明质酸结合细胞在体外活化后持续存在,并具有记忆表型(CD 122(+)CD 44(hi))。这种透明质酸结合的人口增加后,培养与IL-7或IL-15和增殖速度比非结合细胞。在体内,脾和BM中约20-30%的抗原特异性OT-I CD 8(+)记忆T细胞结合透明质酸。Hybryonan结合鉴定了在IL-7和IL-15中增殖更快的记忆细胞,并富集了CD 62 L(+)中央记忆细胞。在体内稳态增殖诱导透明质酸结合的一小部分最迅速分裂的细胞后,几个细胞分裂。这项研究表明,透明质酸结合是诱导抗原诱导的T细胞活化,并发生在最增殖的活化和记忆T细胞的百分比。
CD44 is expressed on T cells where its ability to bind hyaluronan is tightly regulated. Here, we investigated when T cells bind hyaluronan during an immune response. We found that naive, murine T cells do not bind fluoresceinated hyaluronan but are induced to bind upon antigen-induced T-cell activation in vitro and in vivo. Hyaluronan binding occurred on proliferating T cells and the percentage of hyaluronan-binding cells correlated with the strength of the activation stimulus. A small percentage of hyaluronan-binding cells persisted after in vitro activation and had a memory phenotype (CD122(+)CD44(hi)). This hyaluronan-binding population increased after culture with IL-7 or IL-15 and proliferated more rapidly than nonbinding cells. In vivo, approximately 20-30% of antigen-specific OT-I CD8(+) memory T cells in the spleen and BM bound hyaluronan. Hyaluronan binding identified memory cells that proliferated faster in IL-7 and IL-15, and enriched for CD62L(+) central memory cells. In vivo homeostatic proliferation induced hyaluronan binding on a small percentage of the most rapidly dividing cells after several cell divisions. This study demonstrates that hyaluronan binding is induced upon antigen-induced T-cell activation and occurs on a percentage of the most proliferative activated and memory T cells.