Ruiz P, Zacharievich N, Hao L, Viciana A L, Shenkin M
Department of Pathology, University of Miami School of Medicine, Miami, Florida, 33101, USA.
Clin Immunol Immunopathol. 1998 Aug;88(2):156-68. doi: 10.1006/clin.1998.4550.
The nonintegrin receptor CD26, also known as dipeptidyl peptidase IV (DPP IV) is a transmembrane 110- to 120-kDa serine aminopeptidase glycoprotein with multiple functions, including cellular trafficking through extracellular matrix, and costimulatory potential during T cell activation, and is an influence upon T cell differentiation during their maturation in the thymus. In order to further define the expression and functional activity of this membrane exopeptidase in human thymus, we utilized a nondisruptive, cytofluorogenic assay which allowed simultaneous measurement of intracellular DPP IV activity using a fluorochrome-conjugated peptide substrate with surface staining of plasma membrane-associated T lymphocyte lineage antigens CD4 and CD8, as well as CD26. Human thymi were examined using the three-color assay, and significant differences in time-dependent DPP IV activity were found among the thymocyte subsets defined by their CD4/CD8 phenotype. In this regard, CD4(-)/CD8(-) thymocytes displayed the lowest DPP IV activity and had higher activity than the smaller-sized CD26(+) cells. Thymocytes containing greater percentages of apoptotic cells expressed lower DPP IV activity than viable cells. Thus, DPP IV appears to be upregulated as thymocytes mature and is reduced among thymocyte populations enriched for cells undergoing programmed cell death, suggesting that CD26-associated enzymatic activity is ontogenically controlled during T cell maturation and may be involved in thymic deletion of emerging clones.
非整合素受体CD26，也称为二肽基肽酶IV（DPP IV），是一种跨膜的110至120 kDa丝氨酸氨基肽酶糖蛋白，具有多种功能，包括通过细胞外基质进行细胞运输、在T细胞活化过程中的共刺激潜力，以及在胸腺中T细胞成熟过程中对其分化产生影响。为了进一步确定这种膜外肽酶在人类胸腺中的表达和功能活性，我们采用了一种非破坏性的细胞荧光测定法，该方法允许使用荧光染料偶联的肽底物同时测量细胞内DPP IV活性，并对质膜相关的T淋巴细胞谱系抗原CD4、CD8以及CD26进行表面染色。使用三色测定法检查人类胸腺，发现在由其CD4/CD8表型定义的胸腺细胞亚群中，DPP IV活性存在时间依赖性的显著差异。在这方面，CD4（-）/CD8（-）胸腺细胞显示出最低的DPP IV活性，并且比较小的CD26（+）细胞具有更高的活性。含有更高百分比凋亡细胞的胸腺细胞比活细胞表达更低的DPP IV活性。因此，随着胸腺细胞成熟，DPP IV似乎被上调，而在富含经历程序性细胞死亡的细胞的胸腺细胞群体中则降低，这表明与CD26相关的酶活性在T细胞成熟过程中受到个体发育的控制，并且可能参与新出现克隆的胸腺清除。
