Figure 5
Atorvastatin treatment inhibits proliferation of T cells in vivo . (a) Atorvastatin (AT) dose-dependently inhibits proliferation of both differentiated T-helper type (Th)-1 and Th2 cells. Naïve T cells from interleukin (IL)-4-reporter (IL-4 green fluorescent protein-enhanced transcript (4GET)) mice were stimulated with 0.5 μg/ml αCD3 in the presence of 20 μg/ml αIL-4 and 5 ng/ml IL-12 (Th1 condition, left panel) or 50 μg/ml α-interferon (IFN)-γ and 50 ng/ml IL-4 (Th2 condition, right panel). Respective polarization of T cells was confirmed at day 5. Differentiated T cells were then washed and re-stimulated with the indicated concentrations of αCD3 in the presence of 0, 1 or 10 μM AT. T-cell proliferation was assessed by H3 incorporation. Shown is one representative out of three independent experiments. (b) T cells isolated from IL-4-reporter (4GET) mice treated with 10 mg/kg/day AT for 12 days starting 2 days prior to immunization were evaluated for proliferation following activation with the indicated dose of αCD3. (c) IL4-reporter (4GET) mice were immunized with myelin basic protein Ac 1–11. Starting 2 days prior to immunization, mice were fed daily with 10 mg/kg/day AT for 12 days. Twenty-four hours before T-cell isolation, mice were injected intraperitoneally with 200 μl of a 10 mg/ml bromodeoxyuridine (BrdU) solution. BrdU incorporation of freshly isolated, splenic T cells was evaluated by fluorescence-activated cell sorting staining for CD3 and BrdU. Five mice/group were used. Shown is one representative finding out of three independent experiments performed. cpm, counts per minute.