T-cell–derived IL-10 is increased in mice that have relapsed after SCT and is associated with exhaustion. MM-bearing or naive (MM-free; green) recipients were transplanted as previously described with BM+T grafts from FoxP3-RFP × IL-10-GFP reporter B6 donors. MM-bearing mice were categorized as MM-relapsed (purple) or MM-controlled (orange) at 8 weeks after SCT. Mice were sacrificed, BM and spleen were harvested, and T cells were analyzed using flow cytometry. (A) Representative FACS plots of IL-10 and FoxP3 expression in CD8⁺ and CD4⁺ T cells in the BM. (B) Frequency of IL-10–producing CD8⁺ T cells in BM and spleen (n = 16-17 combined from 4 experiments). (C) Spearman r correlation of IL-10⁺CD8⁺ T cells with MM burden in BM (n = 32 combined from 4 experiments). (D) Frequency of IL-10–producing CD4⁺ T cells in BM and spleen (n = 8 – 12 combined from 3 experiments). (E) Spearman r correlation of IL-10⁺CD4⁺ T cells with MM burden in BM (n = 32 combined from 4 experiments). (F-G) Concatenated histograms of TIGIT and PD-1 expression on IL-10⁺ and IL-10⁻ cells in CD4⁺FoxP3⁻, CD4⁺FoxP3⁺ (T_reg) and CD8⁺ T-cell subsets. Geometric mean fluorescence intensity of TIGIT (F) and PD-1 (G) in BM of MM-relapsed mice (n = 8 combined from 3 experiments). Data represent mean ± SEM. *P < .05, **P < .01, ***P < .001 (Mann-Whitney U test).