An α-GalCer–pulsed whole leukemia cell vaccine protects against acute leukemia and is dependent on CD4⁺ and CD8⁺ T cells and langerin⁺CD8α⁺ DCs. A vaccine comprising α-GalCer–pulsed irradiated C1498 cells was administered intravenously 7 days before C1498 challenge. (A) BM histology, (B) peripheral blood smear, and (C) peripheral white blood cell counts were performed at symptom onset in unvaccinated animals, 40 days after C1498 challenge in vaccinated animals, and in naïve control mice. (D) Kaplan-Meier plot showing symptom-free survival of vaccinated and unvaccinated mice after leukemia administration on day zero. Statistical analysis compared unvaccinated and vaccinated with α-GalCer–pulsed irradiated leukemia cell groups. (E) Kaplan-Meier plots showing symptom-free survival of mice vaccinated with leukemia/α-GalCer and challenged with C1498 at day zero. (C-E) Symbols represent treatments: unvaccinated (●), nonleukemic and nonvaccinated (◆), vaccinated with α-GalCer–pulsed irradiated leukemia cells (▪), vaccinated with unpulsed irradiated leukemia cells (□), vaccinated with free α-GalCer (△), depletion of CD4⁺ cells (▲), and depletion of CD8⁺ cells (▼). Statistical analyses compared the depletion groups to mice vaccinated with α-GalCer–pulsed irradiated leukemia cells. (F) lang-EGFPDTR mice were prophylactically vaccinated, and 1 group was administered DT. Symbols represent treatment groups: unvaccinated (●), prophylactic α-GalCer vaccination (▪), and prophylactic vaccination and DT treatment (▲). Symptom-free survival was analyzed and is graphed. *P < .05 (1-way analysis of variance [ANOVA] with a Bonferroni posttest). (A-C) represent a single experiment, (D) represents 3 experiments, and (E-F) represent 2 experiments; 5 mice per group were used for each experiment. *P < .05; **P < .01; ***P < .001 (Mantel-Cox log-rank test).