Figure 1. mTOR inhibition reverses disease in lupus-prone NZB/W mice.

(A) NZB/W mice were monitored for urine protein levels using colorimetric reagent strips for urinalysis. Rapamycin treatment (rapa; 20 mg/kg/mouse) was initiated at the indicated age and continued twice weekly for the remainder of the experiment. Control mice were deemed moribund at week 33, and were sacrificed (Sac.). Protein scores were graded on a semiquantitative scale: 1≥, 30 mg/dl protein; 2≥, 100 mg/dl; 3≥, 300 mg/dl; and 4≥, 2,000 mg/dl. (B) Titers of dsDNA-specific serum IgG were determined using ELISA. Data represent mean ± SEM and are representative of 2 separate experiments each using 4–6 mice per group. *P < 0.05 (A) and *P < 0.01 (B) as determined using Student’s t test. (C) Cells from the indicated organs were applied to dsDNA-coated ELISPOT plates. Shown are numbers of IgM (C) and IgG (D) anti-DNA-secreting plasma cells (PCs). Control mice were analyzed prior to rapamycin-treated mice due to advanced disease; therefore, the data were normalized to numbers of plasma cells per 10⁶ cells. Dots represent values for individual mice, and horizontal lines indicate means. *P < 0.05 as determined by Student’s t test comparing control mice with rapamycin-treated mice within the same organ.