The Chemokine Receptor CX3CR1 Defines Three Antigen-Experienced CD8 T Cell Subsets with Distinct Roles in Immune Surveillance and Homeostasis

• Published in: Immunity (Cambridge, Mass.) Mass.), 2016-12, Vol.45 (6), p.1270-1284
• Main Authors: Gerlach, Carmen, Moseman, E. Ashley, Loughhead, Scott M., Alvarez, David, Zwijnenburg, Anthonie J., Waanders, Lisette, Garg, Rohit, de la Torre, Juan C., von Andrian, Ulrich H.
• Format: Article
• Language: English
• Subjects: Animals; Antigens; CD8-Positive T-Lymphocytes - immunology; Cell Separation; CX3C Chemokine Receptor 1; Cytotoxicity; Experiments; Flow Cytometry; Homeostasis - immunology; Immunologic Memory - immunology; Immunologic Surveillance - immunology; Infections; Lymphocytes; Medical research; Mice; Mice, Inbred C57BL; Pathogens; Receptors, Chemokine - immunology; T cell receptors; T-Lymphocyte Subsets - immunology; Viral infections
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2016.10.018

Infections induce pathogen-specific T cell differentiation into diverse effectors (Teff) that give rise to memory (Tmem) subsets. The cell-fate decisions and lineage relationships that underlie these transitions are poorly understood. Here, we found that the chemokine receptor CX3CR1 identifies three distinct CD8+ Teff and Tmem subsets. Classical central (Tcm) and effector memory (Tem) cells and their corresponding Teff precursors were CX3CR1– and CX3CR1high, respectively. Viral infection also induced a numerically stable CX3CR1int subset that represented ∼15% of blood-borne Tmem cells. CX3CR1int Tmem cells underwent more frequent homeostatic divisions than other Tmem subsets and not only self-renewed, but also contributed to the expanding CX3CR1– Tcm pool. Both Tcm and CX3CR1int cells homed to lymph nodes, but CX3CR1int cells, and not Tem cells, predominantly surveyed peripheral tissues. As CX3CR1int Tmem cells present unique phenotypic, homeostatic, and migratory properties, we designate this subset peripheral memory (tpm) cells and propose that tpm cells are chiefly responsible for the global surveillance of non-lymphoid tissues. [Display omitted] •CX3CR1 correlates with the degree of effector CD8+ T cell differentiation•CX3CR1 delineates three Tmem populations with distinct homeostatic properties•Effector memory T cells are largely excluded from peripheral tissues•CX3CR1int cells are the predominant Tmem subset surveying peripheral tissues Gerlach et al. (2016) demonstrate that CX3CR1 identifies three distinct CD8+ effector and memory T cell (Tmem) subsets. CX3CR1 correlated with the degree of effector differentiation. Surprisingly, a newly identified CX3CR1int Tmem population, not effector memory cells (CX3CR1hi), was the predominant subset that surveyed non-lymphoid tissues.