Dock8 regulates shape integrity and survival of T_RM cells in vivo to control viral skin disease. (A) Numbers of WT and Dock8-deficient HSV-specific gBT-I T cells in the spleen, brachial LNs and skin, 7 d after adoptive transfer (1:1 mixture) into WT recipient mice and HSV infection. (B) Relative numbers of WT gBT-I and Dock8-deficient cpm gBT-I T cells in spleen and infected skin, quantified by flow cytometry at the indicated times after infection. (C) Numbers of WT and Dock8-deficient gBT-I T cells in the spleen at various times after skin infection. (D) Two-photon imaging of skin in C on day 17 after infection. White arrows, Dock8-deficient cells. (E) Numbers of WT and Dock8-deficient gBT-I T cells in skin (CD103⁺ CD69⁺ T_RM) in C. (F) Numbers of WT and Dock8-deficient skin (CD103⁺ CD69⁺) T_RM, at 23 d after intradermal cotransfer of in vitro–activated CD8 T cells into WT recipient mice. (G) Proportions of CD103⁺ CD69⁺ gBT-I T_RM that were WT or Dock8^−/− in skin in F. (H) Impaired control of HSV skin infection by virus-specific memory cells. WT mice received no cells (control) or in vitro activated effector CD8 T cells from WT gBT-I or Dock8-deficient cpm gBT-I mice. After topical treatment with DNFB, mice were infected at the same site 30 d later with HSV and viral titers measured on day 5. Bar, 100 µm. A–C and E–H show means ± SD. For A, data were pooled from four experiments with a total of 20 mice per group. For B, C, and E, data were pooled from four experiments for the day 7 and 31 time points and two experiments for the day 14 time point, with a total of 10–20 mice per time point. F and G are representative of three experiments with seven mice per group. For H, data are from three experiments with a total of 13–15 mice per group. Two-way ANOVA was performed for A–C and E, unpaired two-tailed Student’s t test for F and G, and one-way ANOVA for H. Statistical significance indicated by **, P < 0.01; ***, P < 0.001; ****, P < 0.001; ns, nonsignificant.