Abstracts (complete list) - Wissenschaft Online

Sandra Ehser, Jing-Jing Chuang, Lucian Jiga, Christian Kleist, Flavius Sandra-Petrescu,
Gerhard Opelz, Peter Terness
Generation of tolerogenic dendritic cells by treatment with
Mitomycin C
Dendritic cells (DCs) are the most potent antigen-presenting cells and play a central
role in initiation of immunity or tolerance. Their controlling abilities offer possibilities for
modulation of immune responses in an antigen-specific manner in organ transplantation
or autoimmune diseases. To this end, either naturally suppressive DC subpopulations or
ex vivo manipulated cells can be used. A series of pharmacological agents have been
shown to alter the properties of DCs. We showed that after a short in vitro treatment
with the akylating drug mitomycin c (MMC) DCs acquire tolerogenic properties. They
irreversibly suppress allogeneic T cell responses in vitro and the treatment of recipients
with MMC-incubated donor DCs strongly prolongs heart allograft survival in rats. In
order to elucidate the mechanism of suppression we analyzed the supernatants of MMC-
DCs. They did not mediate any suppressive effect. Therefore, the lacking T cell response
could not be explained by secreted molecules. For this reason next we looked at the
gene expression profile of MMC-treated cells. Over 47,000 transcripts and variants were
analyzed by Affymetrix array, revealing 100 constantly modified gene expressions.
Intriguingly, we found that one gene cluster was involved in apoptosis and another one
– as shown in previous studies - in mediation of tolerance. It has been held that
necrotic cells stimulate, whereas apoptotic cells sometimes inhibit the immune
response. Our studies indicate that MMC induces apoptosis and upregulates tolerogenic
molecules, thus, converting DCs into inhibitory cells. MMC-DCs might offer a therapeutic
tool for antigen-specific suppression of unwanted immune reactions in clinical settings.