NR AUTB
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 TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Poster: Therapie THE-07
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. We have been able to show that multiple administrations of CpG-ODN lead to a significant increase in Th1-associated Ig isotype IgG2c in CpG-ODN-treated mice in comparison to controls with distinct time and frequency correlation and in the absence of additional stimuli, indicating 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.
Taking the essential role of the spleen in prion pathogenesis and shaping of the immune response into account, we analyzed the effects of multiple CpG-ODN administrations on the spleen. We observed an increase in megakaryocytes in the CpG-ODN-treated groups. Furthermore, we found an increase in spleen weights (splenomegaly) correlating with time and frequency of CpG-ODN administrations. Detailed morphometric studies on the ratio of white pulp area/ red pulp area revealed that the observed splenomegaly was due to an expansion of the red pulp. 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. Further studies are currently being conducted to investigate principles underlying the effect of multiple CpG-ODN administration on prion disease in mice.
AD Sabine Ebner, Shneh Sethi, Armin Giese, Christian Hinske, Hans A. Kretzschmar, Center for Neuropathology and Prion Research, Ludwig-Maximilians Universität München, Feodor-Lynen-Strasse 23, 81377 München, Germany
SP englisch
PO Deutschland
EA Übersicht, oben, Details 1, unten, Details 2
OR Tagungsband