NR ATNH
AU Ebner,S.; Sethi,S.K.; Giese,A.; Hinske,C.; Kretzschmar,H.A.
TI Basic principles underlying the effect of multiple administrations of CpG-Oligodeoxynucleotides on prion disease in mice
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Human prions, risk of blood products, and therapy HUMAN-05
PT Konferenz-Poster
AB CpG-Oligodeoxynucleotides (CpG-ODN) containing unmethylated CpG motifs activate cells of the innate immune system. Multiple administrations of 32 µg (5nmol) CpG-ODN per administration lead to a significant increase in the incubation time of prion inoculated mice housed in routine laboratory clean conditions. Immunological effects of multiple administrations of CpG-ODN have not yet been investigated. Therefore, we examined the effect of multiple administrations of CpG-ODN on Ig isotype induction and on spleen architecture, using identical experimental conditions as were used in the original experiments showing the anti-prion effect of multiple CpG-ODN administrations. We show that multiple administrations of CpG-ODN lead to a significant increase in Th1-associated Ig isotypes in CpG-ODN-treated mice in comparison to controls with distinct time and frequency correlation and in the absence of additional stimuli. Regarding spleen architecture, we found a significant increase in megakaryocytes. However, we could not find any significant changes in the number of white-pulp follicles and FDC-M1+ networks per total area of spleen sections. Our results so far do not provide evidence for the assumption that changes in spleen architecture underlie the observed anti-prion effect of multiple CpG-ODN administrations. Furthermore, our results indicate that multiple administrations of CpG-ODN lead to polyclonal activation of B cells. This could account for observed anti-prion effects, however, induction of autoimmunity cannot be excluded. Further studies, including the microarchitecture of FDC-nerve interaction are being conducted to examine principles underlying the anti-prion effect of multiple CpG-ODN administrations.
AD Sabine Ebner, Shneh Sethi, Armin Giese, Christian Hinske, Hans Kretzschmar, Center for Neuropathology and Prionresearch, Ludwig-Maximilians Universität München, Germany
SP englisch
PO Deutschland