Normal, uninfected SJL mice have highly variable spontaneous activity which is not influenced by any treatment.

<p>Three groups of 5 uninfected SJL mice were placed in AccuScan activity monitoring boxes. Baseline measurements were collected over 8 days. After the treatment mice were monitored continuously over 8 weeks. None of the treatments induced changes in either horizontal (A, C, E and G) or vertical (B, D, F and H) activity. The pointwise 95% confidence bands are given for each day.</p

Length of the spontaneous activity monitoring in published studies compared to current study.

<p>Length of the spontaneous activity monitoring in published studies compared to current study.</p

Comparison of three treatments at 90dpi by using predicted model values.

<p>Statistical analysis was performed for each day before and after the treatment. Horizontal nocturnal activity of rHIgM12-treated mice as compared to control IgM- and saline-treated mice significantly diverged/improved on day 7 (p = 0.045) and day 11 (p = 0.042) post-treatment, respectively (denoted by black arrows). The pointwise 95% confidence bands are given for each day.</p

Comparison of three treatments at 45dpi by using predicted model values.

<p>Statistical analysis was performed for each day before and after the treatment. A, C) Horizontal nocturnal activity of rHIgM12-treated mice as compared to control IgM- and saline-treated mice significantly diverged on day 13 (p = 0.015) and day 9 (p = 0.036) post-treatment, respectively. B, D) Vertical (rearing) activity of rHIgM12-treated mice diverged/improved on day 14 (p = 0.019) and day 6 (p = 0.037) post-treatment, respectively. E, F) Comparisons of control IgM- vs. saline-treated mice did not reveal major biological changes neither for horizontal (E) nor for vertical (F) activity. Black arrows denote days with onset of significant improvement. The pointwise 95% confidence bands are given for each day.</p

rHIgM12 improves both horizontal and vertical activity in SJL mice when given early in the disease.

<p>Three groups of 5 SJL mice at 45dpi were placed in AccuScan activity monitoring boxes. Baseline measurements were collected over 8 days. After the treatment mice were monitored continuously over 8 weeks. Panels A, C, E and G correspond to horizontal activity and B, D, F and H correspond to vertical activity. A, B) Original, unfiltered recordings for horizontal and vertical activity; C, D) Average nocturnal activities presented as bins for each day, E, F) Gaussian filtering (GB = 2 days) and G, H) 6^th order polynomial fitting of standardized Z-values revealed improvement in both horizontal and vertical activity in rHIgM12-treated group. Control IgM- and saline-treated groups showed similar levels of motor activity throughout the study. The pointwise 95% confidence bands are given for each day.</p

Example of spontaneous nocturnal activities of TMEV infected mice.

<p><b>A)</b> Original complete recordings of horizontal activity over the period of 64 days. High nocturnal and low diurnal activities are easy to appreciate. Because mice are normally active during the night time we selected nocturnal activities for analysis (6PM-6AM). However, by visual inspection of unfiltered compressed recordings in either horizontal (B) or vertical (C) activity it may be difficult to identify real long-term changes.</p

A single i.p. dose of neuron-binding antibody (rHIgM12) improves horizontal activity in chronically infected SJL mice.

<p>Three groups of 5 SJL mice at 90dpi were placed in AccuScan activity monitoring boxes. Baseline measurements were collected over 8 days. After the treatment mice were monitored continuously over 8 weeks. Panels A, C and E correspond to horizontal activity and B, D and F correspond to vertical activity. A, B) Average nocturnal activities presented as bins for each day suggested the improvement in horizontal activity only in rHIgM12-treated group; C) Gaussian filtering (GB = 2 days) and E) 6^th order polynomial fitting of standardized Z-values provided a clear and distinct improvement in rHIgM12-treated mice. B, D and F) Vertical activity was not affected by any treatment. Activity (vertical scale) is the number of beam interruptions per hour. Parameter GB can be interpreted as a value (in days) of the filter half width at the half height. With the increase of GB value the standard deviation decreases. The pointwise 95% confidence bands are given for each day.</p

B7-DC XAb-induced Tumor Protection is Dependent on CD40.

<p>Wild type or CD40−/− mice were implanted with B16 or WEHI tumor (5×10⁵ cells) and received control antibody or B7-DC XAb by intravenous administration. The mice were monitored for tumor growth and were euthanized if tumor size reached 17×17 mm. Tumor-free B16-implanted mice were monitored regularly for more than 90 days; tumor-free WEHI-implanted mice were monitored regularly for more than 60 days. The scores indicate the number of mice in the indicated treatment group remaining free of tumor. n.s. = not significant.</p

CD40 is required for the DC^XAb-induced generation of anti-tumor CTL responses in vivo.

<p>Wild type or CD40^−/− mice were engrafted with B16 melanoma (A) or WEHI-3 leukemia (B) and treated intravenously with 30 µg B7-DC XAb or control antibody. On day 7, cells from draining lymph nodes were used as effectors in CTL assays. (A) CTL against ⁵¹Cr-labeled B16 tumor targets (Left) or unrelated EL-4 controls (Right). Filled squares show CTL for wild-type mice receiving B7-DC XAb. (B) CTL against ⁵¹Cr-labeled WEHI-3 tumor targets (Left) or unrelated, MHC-matched P815 controls (Right). Filled triangles show the CTL response from wild type mice receiving B7-DC XAb. Symbols and lines for all other treatment groups are nearly superimposable. The results shown are representative of 2 experiments.</p

CD40 is rapidly recruited into complexes containing MHC MHC class II on dendritic cells treated with B7-DC XAb.

<p>(A) DCs were pre-stained with APC-labeled antibody against MHC class II and PE-labeled antibody against CD40 for 15 min. An aliquot of cells was analyzed by flow cytometry (0 min time point). The remaining cells were then treated with 10 µg/ml IgM control antibody (filled histograms) or B7-DC XAb (open histograms). Cells were sampled at the indicated time points and analyzed for a FRET (FL3 channel). (B) Lysates were prepared from untreated DC (0′) or DC treated with control antibody or B7-DC XAb for the indicated times and subjected to immunoprecipitation using an antibody against MHC class II. The resultant complexes were resolved by SDS-PAGE, transferred to PVDF membrane, and probed for CD40. IgH serves as a loading control. The results shown are representative of 2 experiments.</p