CD27⁺cells are essential for the immune control of EBV viral loads and tumorigenesis during EBV infection. (A) Workflow of CD27 depletion experiments. HuMice mice were infected (IP) with 10⁵ RGU B95-8 EBV. At week 2 after EBV infection, animals were injected (IP) with 12.5 μg/g of either anti-CD27 depletion antibody or isotype control antibody consecutively every 4 days to ensure the depletion effect until termination of experiment. (B-E) Frequency of CD3⁺ T cells in anti-CD27 depleting antibody–treated group (α-CD27 depl.) and isotype control antibody–treated group (IsoCtrl. depl.) (B), frequency of CD3⁺ T cells at the termination of the experiment (C), total CD3⁺ T-cell count (D), and tumor burden in the respective groups (E). (F-H) EBV viral loads quantified by quantitative PCR over time (F) and at termination of the experiment in peripheral blood (G) and spleen (H). The lower limit of quantification of 122 IU/mL is depicted as horizontal dashed line. (I-J) Immunohistochemistry images of EBNA2 in the respective groups (original magnification ×200) (I), and the quantification of EBNA2⁺ cells/mm² in splenic sections (J). Images are representative from 1 of 2 independent experiments. Data (n = 8-13 per group) pooled from 2 independent mouse experiments were graphed (B-H,J) and displayed with median and interquartile range. Two-way ANOVA analysis and Sidak’s multiple comparisons as a post hoc test (B,E-F), and the Mann-Whitney U test (C-H,J) were used to assess P values. **P < .01, ***P < .001, ****P < .0001. p.i., postinfection. See also related supplemental Figure 2.