Journal Article

Migratory DCs activate TGF-β to precondition naïve CD8⁺ T cells for tissue-resident memory fate

Hamze, Moustafa, Luster, Andrew D., Griffith, Jason W., Marangoni, Francesco, Mempel, Thorsten R., Äijö, Tarmo, Mani, Vinidhra, Chasse, Alexandra Y., Jeffrey, Kate L., Warner, Ross D., Travis, Mark A., Mora-Buch, Rut, Carrizosa, Esteban, Rahimi, Rod A., McEntee, Craig P., Lorant, Alina, Bromley, Shannon K., Lacy-Hulbert, Adam, Sen, Debattama R.

2019

Overview

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 Resting naïve immunological T cells are poised to become tissue-resident memory cells after encounters with TGF-β–bearing dendritic cells. Epithelial resident memory T (eT RM ) cells serve as sentinels in barrier tissues to guard against previously encountered pathogens. How eT RM cells are generated has important implications for efforts to elicit their formation through vaccination or prevent it in autoimmune disease. Here, we show that during immune homeostasis, the cytokine transforming growth factor β (TGF-β) epigenetically conditions resting naïve CD8 + T cells and prepares them for the formation of eT RM cells in a mouse model of skin vaccination. Naïve T cell conditioning occurs in lymph nodes (LNs), but not in the spleen, through major histocompatibility complex class I–dependent interactions with peripheral tissue–derived migratory dendritic cells (DCs) and depends on DC expression of TGF-β–activating α V integrins. Thus, the preimmune T cell repertoire is actively conditioned for a specialized memory differentiation fate through signals restricted to LNs.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Animals / Antigens / Autoimmune diseases / Biological activity / CCR7 protein / CD11c antigen / CD8 antigen / CD8-Positive T-Lymphocytes - immunology / Cell activation / Cell differentiation / Cell migration / Cell Movement / Conditioning / Cytokines / Dendritic cells / Dendritic Cells - immunology / Dendritic structure / Deoxyribonucleic acid / DNA / DNA vaccines / Epidermis / Epidermis - immunology / Epithelium / Exposure / Growth factors / Homeostasis / Immune system / Immunologic Memory / Immunological memory / Individualized Instruction / Inflammation / Inflammatory response / Integrin alphaV - genetics / Integrin alphaV - metabolism / Lymph nodes / Lymph Nodes - immunology / Lymphatic system / Lymphocytes / Lymphocytes T / Major histocompatibility complex / Memory / Mice / Mice, Inbred C57BL / Mice, Transgenic / Nodes / Pathogens / Preconditioning / Priming / Psoriasis / RESEARCH ARTICLE SUMMARY / Sentinel system / Skin / Skin - immunology / Skin diseases / Spleen / Tissues / Transforming Growth Factor beta - metabolism / Transforming growth factor-b / Vaccines