Figure 10.

OX40-induced T reg cell inhibition prevents the conversion of effector T cells into T reg cells. Effect of intratumor agonistic OX40 mAb on adoptively transferred CD4⁺ T lymphocytes. To test whether anti-OX40 mAb given intratumorally can directly affect lymphocytes circulating in nearby lymph nodes, 3.5 × 10⁶ CD4⁺ CD25⁻ OTII cells were injected i.v. in C57BL/6 WT or OX40-KO mice that were either tumor free or bearing MCA203 tumors. After 2 d, OVA protein was injected within the tumor (or s.c. in the flank of tumor-free controls) together with OX86 or control rat IgG. 2 d later, draining lymph nodes were collected and analyzed by flow cytometry. Because tumor bearers can be considered a tolerogenic environment, we tested whether the adoptively transferred OTII cells gain Foxp3 in the course of tolerogenic activation and whether intratumor OX86 can prevent such an event. (A) The percentage of clonotypic OTII cells expressing Foxp3 in all tested conditions (representative dot plots are shown; top). (B) In OX40-KO hosts, intratumor-injected OX86 failed to prevent the gaining of Foxp3 by donor lymphocytes despite their expression of OX40 (percentages are indicated). *, P < 0.05.