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Original Article

Jan Paul Medema^a, Danita H. Schuurhuis^a, Delphine Rea^a, Joost van Tongeren^a, Joan de Jong^a, Sandra A. Bres^a, Sandra Laban^a, René E.M. Toes^a, Mireille Toebes^c, Ton N.M. Schumacher^c, Bellinda A. Bladergroen^b, Ferry Ossendorp^a, J. Alain Kummer^b, Cornelis J.M. Melief^a, and Rienk Offringa^a

^a Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), 2333ZA Leiden, Netherlands
^b Department of Pathology, Free University Hospital, 1007 MB Amsterdam, Netherlands
^c Division of Immunology, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands
Dept. of Immunohematology and Blood Transfusion, LUMC, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.00-31-71-521675100-31-71-5263013

medema{at}mail.medfac.leidenuniv.nl

Dendritic cells (DCs) play a central role in the immune system as they drive activation of T lymphocytes by cognate interactions. However, as DCs express high levels of major histocompatibility complex class I, this intimate contact may also result in elimination of DCs by activated cytotoxic T lymphocytes (CTLs) and thereby limit induction of immunity. We show here that immature DCs are indeed susceptible to CTL-induced killing, but become resistant upon maturation with anti-CD40 or lipopolysaccharide. Protection is achieved by expression of serine protease inhibitor (SPI)-6, a member of the serpin family that specifically inactivates granzyme B and thereby blocks CTL-induced apoptosis. Anti-CD40 and LPS-induced SPI-6 expression is sustained for long periods of time, suggesting a role for SPI-6 in the longevity of DCs. Importantly, T helper 1 cells, which mature DCs and boost CTL immunity, induce SPI-6 expression and subsequent DC resistance. In contrast, T helper 2 cells neither induce SPI-6 nor convey protection, despite the fact that they trigger DC maturation with comparable efficiency. Our data identify SPI-6 as a novel marker for DC function, which protects DCs against CTL-induced apoptosis.

Key Words: granzyme • CTL • survival • CD40 • LPS

© 2001 The Rockefeller University Press

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This article has been cited by other articles:

• Ronchese, F., Hermans, I. F. (2001). Killing of Dendritic Cells: A Life Cut Short or a Purposeful Death?. JEM 194: f23-f26 [Full Text]  

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