DIPEPTIDYL PEPTIDASE-I AND GRANZYME-A ARE COORDINATELY EXPRESSED DURING CD8(-CELL DEVELOPMENT AND DIFFERENTIATION() T)

Dipeptidyl peptidase I (DPPI) is a granule protease that plays a requi site role in processing the proenzyme form of the CTL granule serine p roteases (granzymes),This study assesses DPPI mRNA and enzyme expressi on during T lymphocyte ontogeny and CTL differentiation. The most imma ture CD3(-)CD4(-)CD8(-) thymocytes were found to express > 40-fold hig her levels of DPPI mRNA, although levels of DPPI enzymatic activity in CD3(-)CD4(-)CD8(-) thymocytes were only modestly higher than those se en for CD4(+)CD8(+) or CD4(+)CD8(-) thymocytes. More mature CD8(+)CD4( -) thymocytes and CD8(+) splenocytes expressed significantly higher le vels of DPPI mRNA and enzymatic activity than CD4(+)CD8(+) or CD4(+)CD 8(-) thymocytes. Granzyme A mRNA expression was observed in DPPI expre ssing CD3(-)CD4(-)CD8(-) and CD8(+)CD4(-) thymocytes and was also obse rved in CD8(+)CD4(-) splenocytes; however, expression was not observed in CD4(+)CD8(+) or CD4(+)CD8(-) thymocytes. Both DPPI mRNA and granzy me A mRNA expression in CD8(+) T cells decreased to very low or undete ctable levels during the first 48 h after allostimulation in MLCs. How ever, peak levels of both DPPI and granzyme A expression,pere observed later in the course of CD8(+) T cell responses to alloantigen, with D PPI mRNA expression peaking on either day 3 or day 4 and granzyme A ex pression peaking at the end of a 5-day MLR. These data indicate that D PPI 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.