Horgan K J, Luce G E, Tanaka Y, Schweighoffer T, Shimizu Y, Sharrow S O, Shaw S
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1992 Dec 15;149(12):4082-7.
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.
鉴于黏附在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，以确定发育调控标记CD45R0与黏附受体（五条VLA整合素链）之间的关系。最重要的发现是：1）α3、α5和α6的表达与CD4细胞上的β1密切共同调节，而VLA-α4的调节则明显不同。2）通常被认为是幼稚细胞的CD45R0-细胞，VLA-α3、VLA-α4、VLA-α5、VLA-α6和β1整合素链的表达水平低且均匀；对脐血CD4细胞的研究证实了幼稚细胞上α4和β1的低均匀表达。3）与之形成鲜明对比的是，通常被认为是记忆细胞的CD45R0+细胞，不仅这些整合素的表达总体增加（相对于CD45R0-细胞），而且表现出异质性。当同时分析VLA-α4和β1标记时，显著的异质性就会显现出来。许多CD45R0+细胞显示VLA-α4和VLA-β1的水平都增加；然而，有些细胞主要是VLA-β1或VLA-α4的水平增加。我们假设，在不同微环境中成为记忆细胞的T细胞会使其整合素表型特化，从而获得独特的功能和归巢能力；在此过程中，VLA-4（CD49d）似乎发挥着独特的作用。
