BM CD8⁺ T-cell function declines in MM and is consistently lower than in matched PB. (A-B) Proportion of (A) CD8⁺ and (B) CD4⁺ T cells within BM FSC/SSC-low cells from controls (n = 10), individuals with MGUS (n = 13), asymptomatic MM (asymptomatic; n = 11), or MM at diagnosis (diagnosis; n = 12). (C-D) Proportion of BM FSC/SSC-low cells from indicated groups expressing (C) CD8 or (D) CD4 and IFN-γ, TNF-α, IL-2, all 3 cytokines (multifunctional), or granzyme B, as indicated, after 4 hours stimulation via CD3/CD28 in presence of Brefeldin A. (E-F) Proportion of (E) CD8⁺ and (F) CD4⁺ T cells within BM or PB FSC/SSC-low cells from indicated groups expressing IFN-γ, TNF-α, or IL-2 after 4 hours stimulation as in panels C-D. Proportions within the BM and PB are directly compared for each group individually and for all patients combined. (G-H) Representative contour plots indicate memory phenotypes of BM (G) CD8⁺ and (H) CD4⁺ T cells expressing indicated cytokine (blue) overlaid onto total populations (red). (I-J) Proportions of naïve (NV), CM, EM, and terminally differentiated effector memory (EMRA) BM and PB CD8⁺ and CD4⁺ T cells are summarized at indicated disease stages. For panels A-D, significance was calculated using 1-way analysis of variance (ANOVA) or for panels E-F (bars) and I-J, 2-way ANOVA and Sidak multiple comparison tests; and for panels E-F (circles), paired t test between overall paired samples; ∗P < .05, ∗∗P < .01, ∗∗∗P < .0001, and ∗∗∗∗P < .00001.