Fig. 3: Rescue of genetic leptin deficiency in ob/ob mice by a single dose of GD2T_IF-Leptin cells.

a, Schematic representation of constructs used to generate DKO, GD2T_IF, and GD2T_IF-Leptin cells, DKO: Bcor/Zh3c12a genes double knock out without GD2 CAR expression CD8⁺ T cells; GFP: green fluorescent protein; 2A: P2A autoclevage peptide sequence. b, Illustration depicting GD2T_IF-Leptin cells secreting leptin. c, Experimental design for rescuing leptin deficiency in male ob/ob mice using GD2T_IF-Leptin cells. One million DKO, GD2T_IF, or GD2T_IF-Leptin cells were intravenously transferred into four-week-old ob/ob mice. Body weight, cell kinetics, metabolic phenotyping, Insulin Tolerance Test (ITT), and Glucose Tolerance Test (GTT) were assessed at specified time points. GD2T_IF-Leptin cell distribution, serum leptin levels, and ex vivo restimulation assays were performed at the study endpoint. Age-matched C57BL/6 mice fed a chow diet served as the reference group. d, Simple linear regression analysis of serum leptin levels (log₂) and the percentage of GD2T_IF-Leptin cells in the spleen (n = 8), R² = 0.9063. e, Body weight curves for mice receiving the indicated treatments, n indicates mice numbers. f, Body fat ratio before (week 0) and after (week 8) treatment in the indicated groups (n = 6). g, h, ITT results, including glucose levels (g) and relative area under the curve (AUC) (h) for the indicated groups (n = 6). i, j, GTT results, including glucose levels (i) and relative AUC (j) for the indicated groups (n = 6). k-n, Metabolic phenotyping of mice following treatment, with 48-hour kinetic measurements post-acclimation (n = 6). k, Respiratory exchange ratio (RER). l, Total energy expenditure. m, Accumulated food intake. n, Physical activity. Data represent the mean ± s.e.m. n indicates the number of mice. Exact P values were determined by simple linear regression (d), two tailed paired Student’s t test (f), one-way ANOVA with Tukey’s multiple-comparisons test (h, j), and two-way ANOVA with Bonferroni’s post hoc test (e, g, i, k-n). Source data and exact P values are provided as a Source Data file.