Some naïve T cell fates are sealed Tissue-resident memory T (T _RM ) cells constitute a subpopulation of memory cells that reside in tissues instead of recirculating. CD8 ⁺ epithelial TRM (eT _RM ) cells, which occupy the epithelium of sites like the skin, require transforming growth factor–β (TGF-β) for their development. Mani et al. found that α _V integrin–expressing dendritic cells, which activate and present TGF-β, are key (see the Perspective by Farber). Surprisingly, this interplay did not occur in the skin or draining lymph nodes during T cell priming. Rather, resting naïve CD8 ⁺ T cells interacted with α _V integrin–expressing migratory dendritic cells during immune homeostasis, reversibly preconditioning them to become eT _RM cells upon activation. A potent cytokine is thus controlled in a context-dependent manner and preimmune T cell repertoires may be less uniform than previously presumed. Science , this issue p. eaav5728 ; see also p. 188