Differential expression of VLA-alpha 4 and VLA-beta 1 discriminates multiple subsets of CD4+CD45R0+ "memory" T cells.

Differential expression of VLA-alpha 4 and VLA-beta 1 discriminates multiple subsets of CD4+CD45R0+ "memory" T cells.
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VLA-α 4 和 VLA-β 1 的差异表达可区分 CD4 CD45R0“记忆”T 细胞的多个亚群。

DOI:
10.4049/jimmunol.149.12.4082
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发表时间:
1992
影响因子:
4.4
通讯作者:
S. Shaw
S. Shaw
中科院分区:
医学2区
文献类型:
--
作者:
K. Horgan;G. E. Luce;Y. Tanaka;T. Schweighoffer;Y. Shimizu;S. Sharrow;S. Shaw

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鉴于粘附在T细胞发育中的重要性,我们对CD4 T细胞进行了系统的流式细胞术分析,以确定发育调节标记物CD45R0和粘附受体(5个VLA整合素链)之间的关系。最重要的发现是:1)α 3、α 5和α 6的表达与CD4细胞上的β 1密切共调节,而VLA-α 4的调节是非常不一致的。2)CD45R0-细胞,通常被理解为幼稚细胞,具有VLA-α 3、VLA-α 4、VLA-α 5、VLA-α 6和β 1整联蛋白链的低均一表达;脐带血CD4细胞的研究证实了α 4和β 1在幼稚细胞上的低均一表达。3)与此形成鲜明对比的是,通常被理解为记忆细胞的CD45R0+细胞不仅显示出这些整合素表达的总体增加(相对于CD45R0-细胞),而且还显示出异质性。当同时分析标志物VLA-α 4和β 1时,显示出显著的异质性。许多CD45R0+细胞显示出VLA-α 4和VLA-β 1的水平增加;然而,有些细胞主要是VLA-β 1或VLA-α 4的水平增加。我们假设T细胞在不同的微环境中成为记忆细胞,使其整合素表型特化,从而获得独特的功能和归巢能力;在这个过程中,VLA-4(CD49d)似乎发挥了独特的作用。
Given the importance of adhesion in T cell development, we have undertaken systematic flow cytometric analysis of CD4 T cells to determine relationships between the developmentally regulated marker CD45R0 and adhesion receptors (five VLA integrin chains). The most important findings are that: 1) expression of alpha 3, alpha 5, and alpha 6 are closely coregulated with beta 1 on CD4 cells, while regulation of VLA-alpha 4 is quite discordant. 2) CD45R0- cells, generally understood to be naive cells, have low homogeneous expression of VLA-alpha 3, VLA-alpha 4, VLA-alpha 5, VLA-alpha 6, and beta 1 integrin chains; studies of cord blood CD4 cells confirm the low homogeneous expression of alpha 4 and beta 1 on naive cells. 3) In marked contrast, CD45R0+ cells, generally understood to be memory cells, show not only an overall increase in expression of these integrins (relative to CD45R0- cells) but also heterogeneity. Dramatic heterogeneity is revealed when the markers VLA-alpha 4 and beta 1 are analyzed together. Many CD45R0+ cells show increased levels of both VLA-alpha 4 and VLA-beta 1; however, some have increased levels principally of either VLA-beta 1 or VLA-alpha 4. We hypothesize that T cells becoming memory cells in different microenvironments specialize their integrin phenotype, thereby acquiring distinctive functional and homing capacities; in this process, VLA-4 (CD49d) appears to play a unique role.