Schweighoffer T, Luce G E, Tanaka Y, Shaw S
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Cell Adhes Commun. 1994 Oct;2(5):403-15. doi: 10.3109/15419069409004451.
Integrins mediate leukocyte adhesion to vascular endothelium and thereby influence leukocyte recirculation. We have explored expression by peripheral blood T cells of beta 1 and beta 7 integrins, particularly alpha 4 beta 1 (VLA-4, CD49d), alpha 4 beta 7 (LPAM-1) and alpha 6 beta 1 (VLA-6, CD49f). Integrin expression differs between CD4+ cells and CD8+ cells in that CD4+ cells 1) are more heterogeneous, particularly for alpha 4; 2) express on the average less alpha 4 and beta 7; and 3) express on the average more alpha 6 and beta 1. 2D gel electrophoretic analysis was combined with flow cytometric analysis to determine which integrin chain pairs are expressed by the CD45RO- (naive) and CD45RO+ (memory) subsets of CD4+ cells. CD45RO- (naive) cells express homogeneously at intermediate levels the three integrin pairs alpha 6 beta 1, alpha 4 beta 1 and alpha 4 beta 7. Although 2D gel analysis suggests similar average integrin chain composition for CD45RO+CD4+ (memory) cells, flow cytometric analysis demonstrates multiple subsets of CD45RO+ cells differing markedly from each other and from naive cells in levels of expression of alpha 6 and alpha 4 integrins. There are a minimum of three CD45RO+ subsets: 1) alpha 4 beta 1hi alpha 6 beta 1hi alpha 4 beta 7neg, which comprises the majority of memory cells; 2) alpha 4 beta 7hi alpha 6 beta 1low presumptive gut-homing memory cells; and 3) alpha 6 beta 1hi alpha 4 beta 7neg alpha 4 beta 1neg, a previously unidentified subset expected to have unique migrational-functional properties. Of particular importance in these results are: the expression by CD4+ naive cells of alpha 6 beta 1, alpha 4 beta 1 and alpha 4 beta 7, the overall prominence and regulation of alpha 6 beta 1 on CD4+ cells, and the selective decreases as well as increases in alpha 4 beta 7 and alpha 4 beta 1 during CD4+ memory specialization. Taken together, these results suggest that differential regulation of expression of alpha 4 and alpha 6 integrin chains that accompany naive-to-memory transition in CD4+ cells are instrumental in generating functional subsets of CD4+ memory cells with specialized recirculation abilities.
整合素介导白细胞与血管内皮的黏附，从而影响白细胞再循环。我们研究了外周血T细胞中β1和β7整合素的表达情况，特别是α4β1（VLA - 4，CD49d）、α4β7（LPAM - 1）和α6β1（VLA - 6，CD49f）。整合素在CD4⁺细胞和CD8⁺细胞中的表达存在差异，具体表现为：1）CD4⁺细胞更为异质性，尤其是α4；2）平均而言，CD4⁺细胞表达的α4和β7较少；3）平均而言，CD4⁺细胞表达的α6和β1较多。二维凝胶电泳分析与流式细胞术分析相结合，以确定CD4⁺细胞的CD45RO⁻（初始）和CD45RO⁺（记忆）亚群表达哪些整合素链对。CD45RO⁻（初始）细胞以中等水平均匀表达α6β1、α4β1和α4β7这三对整合素。尽管二维凝胶分析表明CD45RO⁺CD4⁺（记忆）细胞的整合素链平均组成相似，但流式细胞术分析显示CD45RO⁺细胞的多个亚群在α6和α4整合素的表达水平上彼此差异显著，且与初始细胞不同。至少有三个CD45RO⁺亚群：1）α4β1高表达、α6β1高表达、α4β7阴性，这构成了大多数记忆细胞；2）α4β7高表达、α6β1低表达，推测为归巢至肠道的记忆细胞；3）α6β1高表达、α4β7阴性、α4β1阴性，这是一个先前未鉴定的亚群，预计具有独特的迁移功能特性。这些结果中特别重要的是：CD4⁺初始细胞表达α6β1、α4β1和α4β7；α6β1在CD4⁺细胞上的总体突出性和调节作用；以及在CD4⁺记忆细胞特化过程中α4β7和α4β1的选择性降低和增加。综上所述，这些结果表明，在CD4⁺细胞从初始细胞向记忆细胞转变过程中，α4和α6整合素链表达的差异调节有助于产生具有特殊再循环能力的CD4⁺记忆细胞功能亚群。
Zotero 插件