Dipeptidyl Peptidase I and Granzyme A Are Coordinately Expressed During CD8+ T Cell Development and Differentiation

Abstract

AbstractDipeptidyl 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.