Depletion of CD8 T cells by mAb completely abrogates the therapeutic effect of combination therapy. (A) Groups of 5 age-matched BALB/c mice were inoculated with 10⁶ BCL₁ tumor cells intravenously on day 0 and were treated with 5 Gy TBI and anti-CD40 mAb (100 μg intravenously, day 15) as before. To deplete CD8⁺ or CD4⁺ T cells, mice received anti-CD8 (YTS169; 0.5 mg) or anti-CD4 (YTA1.3.2; 1 mg) mAb, respectively, intraperitoneally 1 day prior to treatment and again 2, 5, and 8 days after treatment. Treatment was as indicated. Survival was recorded daily. Depletion of CD4 T cells did not affect the degree of protection over controls, with 80% remaining disease free over day 80. Depletion of CD8 T cells caused the therapeutic effect to be completely abrogated. Similar results were obtained in at least 3 separate experiments. (B) Naive or 5 Gy plus anti-CD40–treated mice (day 35 to 40 after treatment) were injected with 10⁶ fresh BCL₁ cells intravenously. While naive animals succumbed to disease, previously “cured” animals were resistant to lymphoma challenge and remained disease free (more than 100 days).