Functional classification of memory CD8+ T cells by CX3CR1 expression

• Published in: Nature communications Vol. 6; no. 1; p. 8306
• Main Authors: Böttcher, Jan P., Beyer, Marc, Meissner, Felix, Abdullah, Zeinab, Sander, Jil, Höchst, Bastian, Eickhoff, Sarah, Rieckmann, Jan C., Russo, Caroline, Bauer, Tanja, Flecken, Tobias, Giesen, Dominik, Engel, Daniel, Jung, Steffen, Busch, Dirk H., Protzer, Ulrike, Thimme, Robert, Mann, Matthias, Kurts, Christian, Schultze, Joachim L., Kastenmüller, Wolfgang, Knolle, Percy A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.09.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 13/31; 14; 14/19; 14/69; 631/250/1619/554/1834; 631/250/251; 631/250/255/2514; 631/45/612/194; Adenoviridae Infections - immunology; Animals; Arenaviridae Infections - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - classification; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Chromatography, Liquid; Chronic infection; Classification; CX3C Chemokine Receptor 1; CX3CR1 protein; Cytotoxicity; Effector cells; Flow Cytometry; Fractalkine; Gene expression; Gene Expression Profiling; Homing; Humanities and Social Sciences; Humans; Immunological memory; Listeriosis - immunology; Localization; Lymph nodes; Lymphocytes; Lymphocytes T; Lymphocytic choriomeningitis virus; Memory cells; Mice; multidisciplinary; Proteomes; Receptors, Chemokine - immunology; Science; Science (multidisciplinary); Sequence Analysis, RNA; T-Lymphocyte Subsets - classification; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Cytotoxic - classification; T-Lymphocytes, Cytotoxic - immunology; Tandem Mass Spectrometry; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms9306

Localization of memory CD8 + T cells to lymphoid or peripheral tissues is believed to correlate with proliferative capacity or effector function. Here we demonstrate that the fractalkine-receptor/CX 3 CR1 distinguishes memory CD8 + T cells with cytotoxic effector function from those with proliferative capacity, independent of tissue-homing properties. CX 3 CR1-based transcriptome and proteome-profiling defines a core signature of memory CD8 + T cells with effector function. We find CD62L hi CX 3 CR1 + memory T cells that reside within lymph nodes. This population shows distinct migration patterns and positioning in proximity to pathogen entry sites. Virus-specific CX 3 CR1 + memory CD8 + T cells are scarce during chronic infection in humans and mice but increase when infection is controlled spontaneously or by therapeutic intervention. This CX 3 CR1-based functional classification will help to resolve the principles of protective CD8 + T-cell memory. The function of memory CD8 + T cells is often believed to be directly correlated with their localization in tissues. Here the authors show that CD8 + T cells with different proliferative and cytotoxic properties can be distinguished based on their expression of CX3CR1, independently of their tissue localization.