Figure 1.

Differentiation of T_RM in tissue. Priming and differentiation of naïve CD8⁺ T cells take place in the lymph node in contact with monocytes or dendritic cells (DC3) which promote the generation of CD8⁺ T_RM precursors. Through cytokines secretion such as IFN-γ or IL-21, CD4⁺ T cells help CD8⁺ T cells to be fully functional and influence the T_RM differentiation. Primed CD8⁺ T_RM precursor cells reach the inflamed sites where they differentiate into CD8⁺ T_RM. Within the tissue, several cellular components regulate and maintain T_RM cells: DC3 participate in positioning CD8⁺ T_RM cells in an immune niche and promote their survival, DC infiltrating tumors, tumor cells or epithelial cells express integrin α_vβ₆ and α_vβ₈ and transform LAP-TGF-β to active TGF-β. Active TGF-β maintains tissue residence of T_RM cells and initiates CD103 signaling leading to functional and cytotoxic T_RM cells. CD4⁺ T_RM cells have recently been identified and are also present in peripheral tissues and solid tumors where they secrete inflammatory cytokines such as IFN-γ, TNF-α or IL-2.