Figure 2: Collaboration between CD4+ T cells and γδ17 cells is important for the development of arthritis. | Nature Communications

Figure 2: Collaboration between CD4+ T cells and γδ17 cells is important for the development of arthritis.

From: IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2+Vγ6+γδ T cells

Figure 2

(a,b) Suppression of arthritis development in Il1rn−/− mice after treatment with anti-γδ TCR (a) or anti-CD4 (b) mAb. Non-arthritic Il1rn−/− mice at the age of 4 weeks were injected on days 0, 3, 7 and 10 (ages of 28, 31, 35 and 38 days) with anti-γδ TCR mAb (▪, n=10) or isotype-matched hamster IgG (, n=10) (a), or with anti-CD4 mAb (▪, n=10) or isotype-matched rat IgG (, n=9) (b). *P<0.05 versus control IgG, assessed by the χ2-test. (c,d) Non-arthritic Il1rn−/− mice at the age of 20 days were injected with anti-γδ TCR mAb or hamster IgG every 3 days (ages of 20, 23 and 26 days), and mice were killed at the age of 27 days. Representative haematoxylin and eosin-stained sections of ankle joints in non-treated WT mouse (left column, n=6) and Il1rn−/− mouse treated with control hamster IgG (middle column, n=6) or α-γδ TCR mAb (right column, n=5) are shown. Synovial cell proliferation and inflammatory cell infiltration (arrows), bone erosion (arrowheads), fibrin clots (*) and pannus formation (★) in control Il1rn−/− mouse (middle column) are indicated. Scale bars, 100 μm. Tib, tibia; Tal, talus; Cal, calcaneum; Nav, navicular bone; Cun, cuneiform bone (c). (d) The means of histological scores are shown. *P<0.05 versus Il1rn−/− mice treated with hamster IgG. (e,f) Flow cytometry of LN cells from antibody-treated Il1rn−/− mice. Cells were collected from Il1rn−/− mice, 8 days after the first injection with anti-γδ TCR mAb or hamster IgG-treated (e) or 11 days after the first treatment with anti-CD4 mAb or rat IgG (f) or from non-treated WT mice. Cells were stimulated with P/I for 5 h, and then stained for intracellular IL-17. Numbers refer to percentages in CD3ɛ+ cells. (a–f) Data are representative of two independent experiments. (g,h) scid/scid mice at the age of 4 weeks were transferred with γδ T cells from Cd4−/−Il1rn−/− mice (▪, n=8), CD4+ T cells from Tcrd−/−Il1rn−/− mice (, n=9), Thy1.2+ T cells (whole-T cells) from Il1rn−/− mice (▪, n=8) or γδ T cells from Cd4−/−Il1rn−/− mice plus CD4+ T cells from Tcrd−/−Il1rn−/− mice (× , n=13). Incidence of arthritis is shown (g). Flow cytometry of the joint-infiltrating cells of scid/scid mice after 18 weeks of transfer, or age-matched and non-treated WT or Il1rn−/− mice (h). Cells were stimulated with P/I for 5 h, and then stained for intracellular IL-17. Numbers refer to percentage in CD3ɛ+ cells. Data are pooled from g or representative of (h) two independent experiments.

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