Figure 2.
Figure 2. CD8 TRM expand in patients controlling HBV infection. (a and b) Frequencies of CD69+CD103+ as percentages of the CD8 T cell memory (CD45RA−) pool in paired blood and liver biopsies from patients with chronic HBV infection (n = 33; a) and biopsy/resection tissue from healthy (n = 54) or HBV-infected (n = 35) livers (b). (c) Percent intrahepatic CD8 T cells within live singlet lymphocytes and stratified by differentiation/memory subsets (defined in Fig. 1). (d–f) PD-1 expression (percentage and MFI) on circulating (white), intrahepatic CD45RA−CD69−CD103− (gray), and intrahepatic CD45RA−CD69+CD103+ (black) memory CD8 T cells isolated from healthy controls (n = 26; d), patients with CHB (n = 13; e), and comparing intrahepatic CD45RA−CD69+CD103+ CD8 T cells from healthy controls and CHB (f). (g) CD39 expression (percentage) on circulating (white), intrahepatic CD45RA−CD69−CD103− (gray), and intrahepatic CD45RA−CD69+CD103+ (black) memory CD8 T cells isolated from healthy controls (n = 25) or CHB (n = 18). (h) Representative example of PD-1 expression on CD39−/CD39+ CD45RA−CD69+CD103+ CD8 T cells. (i) Representative immunohistochemical staining of PD-L1 (brown) and CD8 (gray) using a paraffin-embedded liver section. Arrow denotes PD-L1 staining on a cell localized in the liver sinusoids. (j–l) Ki67 (%; n = 10; j), CD57 (%; n = 5; k) and granzyme B (MFI; n = 9; l) expression on circulating (white), intrahepatic CD45RA−CD69−CD103− (gray), and intrahepatic CD45RA−CD69+CD103+ (black) on memory CD8 T cells from patients with CHB. Error bars indicate means ± SEM; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; p-values were determined via Wilcoxon Signed-rank t test (a); Mann-Whitney t test (b, c, and f); MANOVA (c); and Kruskal-Wallis test (ANOVA) with a Dunn’s post hoc test for pairwise multiple comparisons (c, d, e, g, j, k, and l).

CD8 TRM expand in patients controlling HBV infection. (a and b) Frequencies of CD69+CD103+ as percentages of the CD8 T cell memory (CD45RA−) pool in paired blood and liver biopsies from patients with chronic HBV infection (n = 33; a) and biopsy/resection tissue from healthy (n = 54) or HBV-infected (n = 35) livers (b). (c) Percent intrahepatic CD8 T cells within live singlet lymphocytes and stratified by differentiation/memory subsets (defined in Fig. 1). (d–f) PD-1 expression (percentage and MFI) on circulating (white), intrahepatic CD45RA−CD69−CD103− (gray), and intrahepatic CD45RA−CD69+CD103+ (black) memory CD8 T cells isolated from healthy controls (n = 26; d), patients with CHB (n = 13; e), and comparing intrahepatic CD45RA−CD69+CD103+ CD8 T cells from healthy controls and CHB (f). (g) CD39 expression (percentage) on circulating (white), intrahepatic CD45RA−CD69−CD103− (gray), and intrahepatic CD45RA−CD69+CD103+ (black) memory CD8 T cells isolated from healthy controls (n = 25) or CHB (n = 18). (h) Representative example of PD-1 expression on CD39−/CD39+ CD45RA−CD69+CD103+ CD8 T cells. (i) Representative immunohistochemical staining of PD-L1 (brown) and CD8 (gray) using a paraffin-embedded liver section. Arrow denotes PD-L1 staining on a cell localized in the liver sinusoids. (j–l) Ki67 (%; n = 10; j), CD57 (%; n = 5; k) and granzyme B (MFI; n = 9; l) expression on circulating (white), intrahepatic CD45RA−CD69−CD103− (gray), and intrahepatic CD45RA−CD69+CD103+ (black) on memory CD8 T cells from patients with CHB. Error bars indicate means ± SEM; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; p-values were determined via Wilcoxon Signed-rank t test (a); Mann-Whitney t test (b, c, and f); MANOVA (c); and Kruskal-Wallis test (ANOVA) with a Dunn’s post hoc test for pairwise multiple comparisons (c, d, e, g, j, k, and l).

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