ApoVs rescue dysregulated T cell proliferation and ameliorate murine lupus. (A) Scheme of 4-week systemic apoV supplementation in MRL/lpr mice. (B) Normalized ratio of apoVs/T cells in circulation and spleen of MRL/lpr mice treated with or without apoVs for 4 weeks in comparison to age-matched MRL/wt mice analyzed by flow cytometry. N = 6 per group. (C) Numbers of CD3+ cells in spleen and mesenteric lymph node (MLN) of MRL/lpr mice treated with or without apoVs for 4 weeks in comparison to age-matched MRL/wt. N = 6 per group. (D, E) Frequency of naïve, central memory (Tcm), effector memory (Tem), and effector CD4+ T cells in spleen of MRL/lpr mice treated with or without apoVs for 4 weeks in comparison to age-matched MRL/wt. N = 6 per group. (F, G) Frequency of IFNγ+CD4+ T cells in spleen and MLN analyzed by flow cytometry, and serum levels of IFNγ measured by ELISA of MRL/lpr mice treated with or without apoVs for 4 weeks in comparison to age-matched MRL/wt. N = 6–11 per group. (H) Frequency of Foxp3+CD4+ T cells in spleen and MLN of MRL/lpr mice treated with or without apoVs for 4 weeks in comparison to age-matched MRL/wt. N = 6 per group. (I) Scheme of long-term systemic apoV supplementation in MRL/lpr mice. (J) Severe proteinuria (>0.3 g/L) onset in MRL/lpr mice treated with or without apoVs for 8 weeks in comparison to age-matched MRL/wt mice. N = 6 per group. (K) Representative hematoxylin and eosin (HE) staining and Masson's trichrome staining of kidney from MRL/lpr mice treated with or without apoVs for 12 weeks in comparison to age-matched MRL/wt mice. Green triangle indicates immune cell infiltration. Yellow triangle indicates eosinophilic material deposition. Black triangle indicates necrotic glomerulus. Black contour indicates crescent formation. Scale bar = 50 μm. (L, M) Size and weight of spleen and MLN of MRL/lpr mice treated with or without apoVs for 12 weeks in comparison to age-matched MRL/wt mice. N = 6 per group. Scale bar = 1 cm. (N) Representative immunofluorescence staining of CD3+ T cells in lung and colon of MRL/lpr mice treated with or without apoVs for 12 weeks in comparison to age-matched MRL/wt mice. Scale bar = 200 μm. (O) Serum levels of anti-dsDNA IgG measured by ELISA from MRL/lpr mice treated with or without apoVs for 4 weeks in comparison to age-matched MRL/wt. N = 5–15 per group. (P) Survival of MRL/lpr mice treated with or without apoVs starting at 8 weeks in comparison to age-matched MRL/wt mice. N = 6 per group. Kruskal-Wallis test and ANOVA was used for comparison among three groups when appropriate. Mantel-Cox test was used for proteinuria and survival analysis. Data are shown as mean ± standard deviation. ns, not significant. *, p < 0.05. **, p < 0.01. ***, p < 0.001. ****, p < 0.0001.