1. Low accessibility to Ag for CTLs leads to low proliferation of effectors.
Low accessibility to Ag for CTLs leads to low proliferation of effectors. Intravital observations in the pancreas of RIP-GPxCX3CR1+/GFP mice from the HI and LO scenarios revealed less interactions between islet-specific P14 CTLs and GFP+ APCs in the HI scenario compared with the LO scenario. (A and B) Still frames from representative recordings for HI (A) (movie S4) and for LO (B) (movie S5). (C) Interactions are quantified as the arrest coefficient (fraction of time spent in a nonmoving state). Data are representative of groups of six mice per treatment. (D and E) APC occupancy by islet-specific CTLs and non–islet-specific CTLs was further analyzed in paraformaldehyde-fixed, frozen pancreas sections from RIP-GPxCX3CR1+/GFP mice receiving HI (D) or LO (E) amounts of non–islet-specific CD8+ T cells (n = 4 mice per group). Bars next to images display fractional occupancy of APCs by the indicated cell type. (F to H) The difference in APC occupancy could not be explained by changes in islet APC subsets, as shown in (F) for macrophages, in (G) for migratory DCs, and in (H) for plasmacytoid DCs (n = 3 to 4 mice per group). (I and J) The low level of APC interactions in the HI scenario likely led to a lower level of proliferation of effectors, as assessed by transfer of CellTrace Violet–stained Ly5.1+ P14 CD8+ T cells. n = 5 mice per group. Results are representative of two independent experiments. Scale bars, 10 μm. Data are means ± SEM. *P < 0.05, two-tailed unpaired Mann-Whitney U tests.
Gustaf Christoffersson et al. Sci. Immunol. 2018;3:eaam6533
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