Figure 3. CD4+ T cell grafts reverse obesity-associated metabolic abnormalities in RAG^null mice.

a) FACS plots analyzing purity of CD3+CD8+ (top) and CD3+CD4+ (bottom) T cells in spleen, SAT, and VAT, 2 wk following transfer into 12 wk old HFD RAG^null recipients. All subsequent experiments were performed 2–4 wk post-transfer and compared to non-transferred, age-matched, HFD RAG^null mice. b) Left panel: body weights (n=5/group) of recipient mice were monitored post-transfer (*p<0.05, t-test, data from one of four similar experiments). Right panel: weights of individual VAT and SAT pads (n=5/group). CD4+ T cell transfer reduces VAT mass (*p<0.05, t-test). c) Adipocyte diameter following transfer of CD4+ or CD8+ T cells into HFD RAG^null mice (n=3 mice/group, *p<0.01, Mann-Whitney). d) CD4+ T cell transfer improves glucose tolerance in HFD RAG^null recipients (n=10/group, *p<0.0001, 2-way ANOVA). e) Fasting glucose (left panel) and insulin (right panel) in CD4+ or CD8+ transferred HFD RAG^null mice (n=5–10 mice/group, *p<0.03, **P<0.01, t-test). f) HFD RAG^null mice reconstituted with CD4+ T-cells show improved insulin tolerance (n=10, *p<0.05, 2-way ANOVA). g) FACS plots of OT2 TCRVα re-rearrangements in spleen and VAT, 2 wk following transfer. The purity of CD4⁺OT2^hi cells transferred was 99.5%. h) CD4+OT2:TCRα^hi (CD4⁺OT2^hi) T cells fail to improve glucose and (i) insulin tolerance following transfer (n=5/group, *p<0.0001, 2-way ANOVA). j) Fasting glucose (left panel) and fasting insulin (middle panel) in CD4+ or CD4+OT2:TCRα^hi (OT2^hi) transferred HFD RAG^null mice (n=5 mice/group, *p<0.05, t-test). Right panel, CD4+OT2^hi:TCRα^hi T cells fail to improve weight post transfer (n=5 mice/group, *p<0.004, t-test).