(A) Antigen-reactive CD4⁺ T cells were gated as CD154⁺CD69⁺ based on the DMSO vehicle control (participant T1DAL-243767). (B and C) The frequency of naive and memory populations in IAR and viral antigen–reactive CD4⁺ T cells in baseline PBMC samples from the treated and placebo groups (n = 18). Enriched antigen-reactive cells were compared with total CD4⁺ T cell populations from the pre-enrichment samples of the same cultures. Stem cell memory (TSCM), central memory (TCM), and effector memory (TEM) are shown as the percentage of antigen-reactive or of total CD4⁺ T cells; each symbol represents a unique individual. (D) The mean frequency of each population from B and C. Asterisks indicate significant differences between IAR and viral antigen–reactive populations. (E and F) The frequencies of enriched IAR and virus-reactive memory CD4⁺ T cells with the indicated T helper phenotypes versus CD4⁺ T cells from the pre-enrichment samples of the same cultures (n = 18). Th1 (CXCR3⁺CCR4^–CCR6^–), Th2 (CCR4⁺CCR6^–), Th17 (CCR6⁺CCR4⁺), and Th1/17 (CXCR3⁺CCR6⁺CCR4^–) are expressed as the frequency of memory antigen-reactive CD4⁺ T cells or total memory CD4⁺ T cells. (G) The mean frequency of each Th subset from E and F. Asterisks indicate significant differences between IAR and viral antigen–reactive populations. Significant differences in B–G were determined using Wilcoxon’s matched-pairs signed-rank test with Benjamini-Hochberg adjustment. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. (H and I) Spearman’s correlation between the frequency of IAR CD4⁺ TCM cells (H) or virus-reactive TCM cells (I) per participant with the rate of C-peptide change in alefacept- and placebo-treated participants. The linear regression line is shown with 95% confidence intervals in dotted lines.