title: Expression of chemokine receptor CXCR3 on T cells affects the balance between effector and memory CD8 T-cell generation.
abstract: Generation of a robust immunological memory response is essential for protection on subsequent encounters with the same pathogen. The magnitude and quality of the memory CD8 T-cell population are shaped and influenced by the strength and duration of the initial antigenic stimulus as well as by inflammatory cytokines. Although chemokine receptors have been established to play a role in recruitment of effector CD8 T cells to sites of inflammation, their contribution to determination of T-cell fate and shaping of the long-lived memory T-cell population is not fully understood. Here, we investigated whether reduced access to antigen and inflammation through alterations in expression of inflammatory and homeostatic chemokine receptors has an impact on generation of effector and memory CD8 T cells. We found that in mice infected with lymphocytic choriomeningitis virus, colocalization of virus-specific CD8 T cells with antigen in spleen is dependent on expression of the inflammatory chemokine receptor, CXCR3. In addition, absence of CXCR3 expression on CD8 T cells leads to formation of fewer short-lived effector cells and more memory precursor cells. Furthermore, the memory CD8 T-cell population derived from CXCR3-deficient cells has fewer cells of the effector memory phenotype and exhibits a recall response of greater magnitude than that of WT cells. These data demonstrate that CD8 T-cell positioning relative to antigen and inflammatory cytokines in secondary lymphoid organs affects the balance of effector and memory T-cell formation and has both a quantitative and qualitative impact on the long-lived memory CD8 T-cell population.
authors.affiliation: Division of Rheumatology, Department of Medicine, and Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, CA 94143, USA.
authors.forename: Joyce K
authors.initials: JK
authors.lastname: Hu
authors.forename: Takashi
authors.initials: T
authors.lastname: Kagari
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Clingan
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Matloubian
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000276:immunology; D007156:Immunologic Memory; D018655:Lymphocyte Count; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D054367:Receptors, CXCR3 / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: C515188:Cxcr3 protein, mouse; D016207:Cytokines; D054367:Receptors, CXCR3