Figure 10.

Ccr4^−/− mice are prone to autoimmune disease. (A) Representative hematoxylin and eosin stains of extraorbital lacrimal gland sections from Ccr4^−/− and Ccr4^+/+ mice at 8–13 mo of age. Arrows indicate lymphocytic infiltrates. (B) Severity of lymphocytic infiltrates in intraorbital and extraorbital lacrimal glands of 8–13-mo-old Ccr4^+/+ or Ccr4^−/− mice, with seven mice analyzed per group. Two-way ANOVA was used to determine if CCR4 or the type of lacrimal gland impacted severity; **, P < 0.01. The significance of CCR4 sufficiency is displayed. (C) Representative images of Rag2^−/− kidney sections immunostained with serum from 8-13-mo-old WT, Ccr4^−/−, or Ccr7^−/− mice. Autoantibodies were detected with anti–mouse IgG (red) and nuclei with DAPI (blue). Bars, 100 µm. Digitally magnified regions are shown in insets to facilitate visualization of colocalization of autoantibodies and nuclei. (D) Proportion of aged mice (8–13 mo) containing serum autoantibodies was quantified, as determined by immunostaining as in C. *, P < 0.05 (Fisher’s exact test). (E) Naive splenic T cells were isolated from Ccr4^+/+ or Ccr4^−/− mice, labeled with CMFDA, and incubated in the presence or absence of irradiated syngeneic splenic stimulator cells. At the indicated time points, the percentage of cells that had undergone at least one cell division was quantified. Mean ± SEM are representative of three experiments with five technical replicates per group. *, P < 0.05 (Student’s t test with Bonferroni correction).