Dipeptidyl peptidase I and granzyme A are coordinately expressed during CD8+ T cell development and differentiation.
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.
Mabee
C L
CL
Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 75235, USA.
McGuire
M J
MJ
Thiele
D L
DL
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D020789:Cathepsin C; D002454:Cell Differentiation; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000378:metabolism*; D053804:Granzymes; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
D007519:Isoantigens; D012333:RNA, Messenger; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D020789:Cathepsin C; D053804:Granzymes; D012697:Serine Endopeptidases