Mabee C L, McGuire M J, Thiele D L
Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 75235, USA.
J Immunol. 1998 Jun 15;160(12):5880-5.
Dipeptidyl peptidase I (DPPI) is a granule protease that plays a requisite role in processing the proenzyme form of the CTL granule serine proteases (granzymes). This study assesses DPPI mRNA and enzyme expression during T lymphocyte ontogeny and CTL differentiation. The most immature CD3- CD4- CD8- thymocytes were found to express >40-fold higher levels of DPPI mRNA, although levels of DPPI enzymatic activity in CD3- CD4- CD8- thymocytes were only modestly higher than those seen for CD4+ CD8+ or CD4+ CD8- thymocytes. More mature CD8+ CD4- thymocytes and CD8+ splenocytes expressed significantly higher levels of DPPI mRNA and enzymatic activity than CD4+ CD8+ or CD4+ CD8- thymocytes. Granzyme A mRNA expression was observed in DPPI expressing CD3- CD4- CD8- and CD8+ CD4- thymocytes and was also observed in CD8+ CD4- splenocytes; however, expression was not observed in CD4+ CD8+ or CD4+ CD8- thymocytes. Both DPPI mRNA and granzyme A mRNA expression in CD8+ T cells decreased to very low or undetectable levels during the first 48 h after allostimulation in MLCs. However, peak levels of both DPPI and granzyme A expression were observed later in the course of CD8+ T cell responses to alloantigen, with DPPI mRNA expression peaking on either day 3 or day 4 and granzyme A expression peaking at the end of a 5-day MLR. These data indicate that DPPI is expressed at all stages of T cell ontogeny and differentiation in which granzyme A mRNA is detected; consequently, DPPI appears to be available for the processing and activation of granzyme A during both CD8+ T cell development and differentiation.
二肽基肽酶I（DPPI）是一种颗粒蛋白酶，在加工细胞毒性T淋巴细胞（CTL）颗粒丝氨酸蛋白酶（颗粒酶）的酶原形式中发挥着必不可少的作用。本研究评估了T淋巴细胞个体发育和CTL分化过程中DPPI mRNA和酶的表达情况。发现最不成熟的CD3-CD4-CD8-胸腺细胞表达的DPPI mRNA水平比其他细胞高40倍以上，尽管CD3-CD4-CD8-胸腺细胞中的DPPI酶活性水平仅略高于CD4+CD8+或CD4+CD8-胸腺细胞。更成熟的CD8+CD4-胸腺细胞和CD8+脾细胞表达的DPPI mRNA和酶活性水平明显高于CD4+CD8+或CD4+CD8-胸腺细胞。在表达DPPI的CD3-CD4-CD8-和CD8+CD4-胸腺细胞中观察到颗粒酶A mRNA的表达，在CD8+CD4-脾细胞中也观察到了颗粒酶A mRNA的表达；然而，在CD4+CD8+或CD4+CD8-胸腺细胞中未观察到表达。在混合淋巴细胞培养（MLC）中同种异体刺激后的最初48小时内，CD8+T细胞中的DPPI mRNA和颗粒酶A mRNA表达均降至非常低或无法检测的水平。然而，在CD8+T细胞对同种异体抗原的反应过程中，随后观察到DPPI和颗粒酶A表达的峰值水平，DPPI mRNA表达在第3天或第4天达到峰值，颗粒酶A表达在5天的混合淋巴细胞反应结束时达到峰值。这些数据表明，在检测到颗粒酶A mRNA的T细胞个体发育和分化的所有阶段都表达DPPI；因此，在CD8+T细胞发育和分化过程中，DPPI似乎可用于颗粒酶A的加工和激活。
