PMID: 9164937Jun 1, 1997Paper

A selective inhibitor of dipeptidyl peptidase I impairs generation of CD8+ T cell cytotoxic effector function

The Journal of Immunology : Official Journal of the American Association of Immunologists
D L ThieleP E Lipsky

Abstract

CTL express high levels of dipeptidyl peptidase I (DPPI), a granule thiol protease able to convert the zymogen precursors of granzymes A and B into active proteases. In the present studies, the effects of specific inhibition of DPPI on generation of CTL effector functions were examined. When T cell DPPI activity was inhibited by >95% throughout 5-day MLC, a significant reduction in the generation of CD8+ T cell BLT esterase activity (<30% of control) and cytolytic activity (<10% of control) was observed. DPPI inhibition during the second to fourth days of 5-day MLC also was associated with reduced proliferation of CD8+ T cells, but had no effect on CD4+ T cell proliferation or IL-2 production by either population. CTL generated in the continuous presence of DPPI inhibition also exhibited impaired lysis of anuclear erythrocyte targets and diminished killing of nucleated targets by perforin-independent pathways. In contrast, inhibition of DPPI during only the last 24 h of 5-day MLC was associated only with reduced generation of BLT esterase activity and reduced lysis of nucleated targets by perforin-dependent pathways. Repeated or delayed inhibition of DPPI in MLC containing granzyme B-deficient responder cells also impaired gene...Continue Reading

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