Figure 3. CD8α does not mark a distinct, terminally differentiated population.

(A and B) Bulk RNA-Seq was performed on freshly isolated (A) CD56^bright or (B) CD56^dim NK cells sorted on the basis of CD8α expression (CD3^–CD19^–CD14^–). Data are shown as the log₂-normalized expression of protein-coding genes in CD8α^+/– cell populations. Red dots indicate genes that were statistically significantly differentially expressed (adjusted P < 0.05). n = 6 unique donors. The R² value was derived from simple linear regression of gene expression data. (C and D). Peripheral blood NK cells were stained for the expression of markers of NK maturation. (C) CD56^dim NK cell maturation stages were identified based on expression of NKG2A, KIR (KIR3DL1, KIR2DL1, and KIR2DL2/3), and CD57, with maturation increasing from left to right. Data are shown as the percentage of each subset that was positive for CD8α expression. n = 28 donors. (D) Expression of CD8α within NKG2A^–CD56^brightKIR^– or KIR⁺ (KIR3DL1⁺, KIR2DL1⁺, and KIR2DL2/3⁺) NK cells. n = 11 donors. Data represent the mean ± SEM. **P < 0.01 and ****P < 0.0001, by (C) 2-way ANOVA with Holm-Šídák correction for multiple comparisons and (D) paired, 2-tailed Student’s t test.