Fig 1: Distribution of leucocytes within different multiple sclerosis lesion areas. (A) Schematic graph of an active multiple sclerosis lesion with a central large inflamed vein, a demyelinated tissue area, containing macrophages with different stages of myelin degradation (green area) and a rim of initial tissue injury (grey zone) characterized by microglia activation, oligodendrocyte injury (loss of myelin associated glycoprotein) and oligodendrocyte apoptosis (‘prephagocytic’ lesion areas; Barnett and Prineas, 2004). The highest density of lymphocytes is seen in the perivascular space of the central vein and most of the B cells in the lesion are present at this site. T cells also diffusely infiltrate the lesion parenchyma (green area). They are also present, but in low numbers, at the site of initial demyelination (grey area; Marik et al., 2007). (B–H) Perivascular (PVA) versus diffuse parenchymal distribution of lymphocyte subsets in multiple sclerosis lesions. When quantification is based on the area of the entire lesion (mm2) most leucocyte subsets (CD3, CD8a, CD8ß, CCR5) are present in both compartments without significant preference. Dominant localization in the perivascular space is seen for B cells (CD20) and to a lower extent for CD4+ T cells. In contrast CD103+ T cells show a trend towards accumulation in the lesion parenchyma. Images for colourblind readers can be found in Supplementary Fig. 5. RRMS = relapsing-remitting multiple sclerosis.
Fig 2: Cellular source of CD103+ cells in ESCC tissues. (A) Double immunofluorescence staining shows CD103 (green), CD3 (red), CD11c (red), CD4 (red), and CD8 (red) expression and co-localization of double-positive cells (yellow) in ESCC tissue. (B) The percentages of CD11c+CD103+ cells identified as CD11c and CD103 double-positive cells and calculated in total numbers of CD103+ cells in the ANT and IT regions. Scale bar = 25 µm. (C, D) The percentages of CD3+CD103+ cells identified as double-positive cells and calculated in total numbers of CD103+ or CD3+ cells in the ANT and IT regions (n = 7). (E, F) The percentages of CD4+CD103+ and CD8+CD103+ cells identified as double-positive cells and compared to the total numbers of CD103+ cells in the ANT (E) and IT regions (F), respectively (n = 10). Results are the means ± SEM (bars); **P < 0.01; ***P < 0.001.
Fig 3: Kaplan–Meier plots for overall survival (OS) according to CD4 (A), CD8 (B), CD103 (C), slan (D), BDCA-2 (E), PD1 (F), PD-L1 (G), TLR3 (H), TLR7 (I), TLR9 (J), and GATA3 (K) expression.
Fig 4: High intratumoral CD103+ cell density is a predictor of favorable prognosis in patients with ESCC. (A) Representative IHC images demonstrate high (left) and low (right) number of CD103+ cells. Brown areas indicate positively stained cells. Scale bar = 50 µm. (B) Kaplan-Meier survival curves compare OS and DFS rates in patients (n = 107) with low or high intratumoral CD103+ cell density in SYSUCC cohort. (C) Kaplan-Meier survival curves compare OS and DFS rates in patients (n = 91) with low or high intratumoral CD103+ cell density in STCH cohort. P < 0.05 was considered statistically significant (log-rank test).
Fig 5: CD103+ cells co-express CTLA-4, granzyme B (GB), and PD-1 in ESCC. (A-C) Double immunofluorescence staining shows CD103, CTLA-4 (A), granzyme B (GB) (B), and PD-1 (C) expression and co-localization of double-positive cells in ESCC tissue. DAPI (blue) was used as a counterstain. Scale bar = 25 µm. The percentages were identified as double-positive cells compared to the total numbers of CD103+ cells in the ANT and T regions, respectively (n = 7). Results are the means ± SEM (bars).
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