MHC class II-mediated apoptosis of mature dendritic cells proceeds by activation of the protein kinase C-delta isoenzyme.

Abstract:

:The mature dendritic cell (DC) is considered to be the most potent antigen-presenting cell. Regulation of the DC, particularly its survival, is therefore critical. Mature DC are markedly more sensitive to HLA-DR-mediated apoptosis than immature DC. To further characterize this key survival difference, we compared the intracellular signals initiated via HLA-DR in mature versus immature DC. Apoptosis was unchanged by inhibition of tyrosine kinases or phosphatases. HLA-DR-mediated re-localization of protein kinase C (PKC)-delta to the nucleus was detected in mature DC by confocal microscopy and by immunoblotting. Activation of PKC-delta in mature DC was revealed by the detection of the PKC-delta catalytic fragment in the nuclear fraction isolated from mature DC which had been stimulated via HLA-DR. The broad-spectrum PKC inhibitor, Calphostin C, as well as the PKC-delta-selective inhibitor, Rottlerin, inhibited HLA-DR-mediated apoptosis of mature cells. Taken together, these data reveal a role for the PKC-delta isoenzyme in regulating HLA class II-mediated apoptosis of mature DC. Thus, the lifespan of the mature DC could be controlled by signals generated in the course of antigen presentation, and thereby prevent DC persistence and prolonged stimulation of T and B lymphocytes.

journal_name

Int Immunol

journal_title

International immunology

authors

Bertho N,Blancheteau VM,Setterblad N,Laupeze B,Lord JM,Drénou B,Amiot L,Charron DJ,Fauchet R,Mooney N

doi

10.1093/intimm/dxf058

subject

Has Abstract

pub_date

2002-08-01 00:00:00

pages

935-42

issue

8

eissn

0953-8178

issn

1460-2377

journal_volume

14

pub_type

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