Expression of the serpin serine protease inhibitor 6 protects dendritic cells from cytotoxic T lymphocyte-induced apoptosis: Differential modulation by T helper type 1 and type 2 cells

Dendritic cells (DCs) play a central role in the immune system as they driv e activation of T lymphocytes by cognate interactions. However, as DCs expr ess high levels of major histocompatibility complex class I, this intimate contact may also result in elimination of DCs by activated cytotoxic T lymp hocytes (CTLs) and thereby limit induction of immunity. We show here that i mmature DCs are indeed susceptible to CTL-induced killing, but become resis tant upon maturation with anti-CD40 or lipopolysaccharide. Protection is ac hieved by expression of serine protease inhibitor (SPI)-6, a member of the serpin family that specifically inactivates granzyme B and thereby blocks C TL-induced apoptosis. Anti-CD40 and LPS-induced SPI-6 expression is sustain ed for long periods of time, suggesting a role for SPI-6 in the longevity o f DCs. Importantly, T helper 1 cells, which mature DCs and boost CTL immuni ty, induce SPI-6 expression and subsequent DC resistance. In contrast, T he lper 2 cells neither induce SPI-6 nor convey protection, despite the fact t hat they trigger DC maturation with comparable efficiency. Our data identif y SPI-6 as a novel marker for DC function, which protects DCs against CTL-i nduced apoptosis.