CD4⁺ T cell–mediated induction of gp38⁺ stromal cell networks enhances lymphoma growth. (A) Rag^−/− mice were reconstituted with 5 × 10⁶ naive CD4⁺ T cells (day −4) and challenged with 1 × 10⁵ Wt Eμ-Myc lymphoma cells. Tumor load in the spleen was assessed 13 days after tumor challenge. Reconstituted Rag^−/− mice 13 days after tumor challenge compared with nontreated controls (n = 6 or 7 mice per group). **P ≤ .01. (B) CD4⁺ T cell–reconstituted Rag^−/− mice exhibited induction of gp38⁺ FRC networks (bottom panel: red represents FRCs; and green, CD11c⁺). Adoptively transferred T cells can also be visualized at this site (bottom panel right: red represents CD3⁺ T cells; n = 5 animals per group). Scale bars represent 100 μm. (C) In vivo blockage of the CD40 signaling pathway by treatment of Rag^−/− mice with 3 × 200 μg anti-CD40L antibody in 5-day intervals starting on day 0, or control hamster antibody (n = 6 mice per group). *P ≤ .05. Rag^−/− mice were reconstituted with 3 × 10⁶ CD4⁺ T and challenged with 2 × 10⁴ tumor cells. At day 13, tumor load in the spleen was assessed by weight.