Fig. 6

Aged CD8⁺ T cells exhibit terminally exhausted phenotype. A, B Aged mice at day 7 p.i. had expanded population of terminally exhausted CD8⁺ T cells (T_EX) in both bulk CD8⁺ T cells and CD8⁺ N11 tet⁺ T lymphocytes. T_EX CD8⁺ T cells are defined as TCF1/7⁻ EOMES⁺ TOX⁺. C Aged CD4 depleted mice expressed similar levels of TOX and EOMES on CD8s compared to isotype treated mice. Young CD4 depleted mice did have a trend towards increased expression of TOX and EOMES on CD8s. D & F A_T—> Y_H accumulated T_EX bulk and HMPV-specific CD8⁺ T lymphocytes to a similar degree as A_T—> A_H control while Y_T—> A_H and Y_T- > Y_H had reduced T_EX populations. E & G A similar T_EX CD8⁺ population in both bulk and epitope-specific CD8⁺ T lymphocytes was seen in the A_{CD8 T}—> Y_H adoptive transfer model. H & I scRNAseq on naive young and aged mice revealed similar expression patterns of TOX and EOMES in CD8⁺ T cells from aged lung. (J-L) Violin plots of TCF7, TOX, and EOMES expression, respectively, in murine lung CD8⁺ T cells in both age groups. M Violin plot of TCF7 expression in PBMCs from healthy aged and young humans. N Representative IFN ELISpot image. O IFN spot number significantly decreased in aged mice. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, unpaired t-test or one-way ANOVA