TY - JOUR
T1 - Dipeptidyl peptidase I and granzyme A are coordinately expressed during CD8+ T cell development and differentiation
AU - Mabee, Christopher L.
AU - McGuire, Michael J.
AU - Thiele, Dwain L
PY - 1998/6/15
Y1 - 1998/6/15
N2 - 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.
AB - 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.
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M3 - Article
C2 - 9637500
AN - SCOPUS:0032526606
VL - 160
SP - 5880
EP - 5885
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -