In vivo accumulation of T cells in response to IL‐2/anti‐IL‐2 mAb complexes is dependent in part on the TNF family ligand 4‐1BBL

Immune complexes combining IL‐2 with particular anti‐IL‐2 antibodies can be used to selectively expand regulatory T cells or memory T cells. Combining IL‐2 with anti‐IL‐2 (Clone S4B6) greatly enhances the biological potency of IL‐2 in vivo leading to selective expansion of CD8 memory T cells and NK cells compared with regulatory T cells. Here we show that in vivo administration of IL‐2/anti‐IL‐2 mAb (IL‐2/mAb) complexes induces 4‐1BB expression on both adoptively transferred antigen‐specific memory CD8 T cells as well as on endogenous memory phenotype cells. Remarkably, the accumulation of adoptively transferred memory CD8 T cells following in vivo IL‐2/mAb‐complex treatment was found to be dependent in part on the presence of 4‐1BBL in the host. These effects were independent of IL‐2‐induced cell division, suggesting that 4‐1BBL‐induced survival signals contribute to IL‐2/mAb‐complex‐induced T‐cell accumulation in vivo.