Journal Article

The developmental pathway for CD103+CD8+ tissue-resident memory T cells of skin

Carbone, Francis R, Stock, Angus T, Stefanovic, Tijana, Hafon, Ming-Li, Vega-Ramos, Javier, Heath, William R, Mueller, Scott N, Mackay, Laura K, Lauzurica, Pilar, Inouye, Michael, Rahimpour, Azad, Tscharke, David C, Ma, Joel Z, Collins, Nicholas, Gebhardt, Thomas

2013

Overview

Long-lived tissue-resident memory T cells (T RM cells) confer fast, robust protection after pathogen rechallenge. Gebhardt and colleagues show that skin T RM cells arise from KLRG1 – cells that differentiate in situ in response to IL-15 and TGF-β. Tissue-resident memory T cells (T RM cells) provide superior protection against infection in extralymphoid tissues. Here we found that CD103 + CD8 + T RM cells developed in the skin from epithelium-infiltrating precursor cells that lacked expression of the effector-cell marker KLRG1. A combination of entry into the epithelium plus local signaling by interleukin 15 (IL-15) and transforming growth factor-β (TGF-β) was required for the formation of these long-lived memory cells. Notably, differentiation into T RM cells resulted in the progressive acquisition of a unique transcriptional profile that differed from that of circulating memory cells and other types of T cells that permanently reside in skin epithelium. We provide a comprehensive molecular framework for the local differentiation of a distinct peripheral population of memory cells that forms a first-line immunological defense system in barrier tissues.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/2152/1566/1571 / Animals / Antigens, CD - genetics / Antigens, CD - immunology / Antigens, CD - metabolism / Antigens, Differentiation, T-Lymphocyte - genetics / Antigens, Differentiation, T-Lymphocyte - immunology / Antigens, Differentiation, T-Lymphocyte - metabolism / Biomedicine / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - metabolism / CD8-Positive T-Lymphocytes - virology / Cell Differentiation - genetics / Cell Differentiation - immunology / Flow Cytometry / Herpes Simplex - immunology / Herpes Simplex - virology / Herpesvirus 1, Human - immunology / Herpesvirus 1, Human - physiology / Host-Pathogen Interactions - immunology / Immunologic Memory - immunology / Immunology / Infectious Diseases / Integrin alpha Chains - genetics / Integrin alpha Chains - immunology / Integrin alpha Chains - metabolism / Interleukin-15 - genetics / Interleukin-15 - immunology / Interleukin-15 - metabolism / Lectins, C-Type - genetics / Lectins, C-Type - immunology / Lectins, C-Type - metabolism / Mice / Mice, Inbred C57BL / Mice, Inbred Strains / Mice, Knockout / Mice, Transgenic / Oligonucleotide Array Sequence Analysis / Protein-Serine-Threonine Kinases - genetics / Protein-Serine-Threonine Kinases - immunology / Protein-Serine-Threonine Kinases - metabolism / Receptors, Immunologic - genetics / Receptors, Immunologic - immunology / Receptors, Immunologic - metabolism / Receptors, Transforming Growth Factor beta - genetics / Receptors, Transforming Growth Factor beta - immunology / Receptors, Transforming Growth Factor beta - metabolism / Reverse Transcriptase Polymerase Chain Reaction / Signal Transduction - genetics / Signal Transduction - immunology / Skin / Skin - immunology / Skin - metabolism / Skin - virology / Tissues / Transcriptome - genetics / Transcriptome - immunology