CD4 and Granuloma: Although granuloma formation is known to be mediated by IFN-γ secreted from CD4+ T cells,29 anti-4-1BB-induced granuloma development seems to be mediated by CD8+ T cells rather than CD4+ T cells, since 4-1BB triggering preferentially enhances the proliferation of and IFN-γ production by CD8+ T cells.28 To investigate whether granuloma formation is mediated by IFN-γ from CD8+ T cells, we assessed anti-4-1BB-mediated granuloma formation in mice by depleting anti-CD8 mAb 10–15 days after injection of MC38 tumor cells.