CXCR3/CXCL10 Axis Shapes Tissue Distribution of Memory Phenotype CD8+ T Cells in Nonimmunized Mice [IMMUNE SYSTEM DEVELOPMENT]

Abstract

The preimmune repertoire consists of mature T lymphocytes that have not yet been stimulated in the periphery. Memory phenotype (MP) cells have been reported as part of the preimmune repertoire (i.e., T cells bearing memory markers despite lack of engagement with cognate Ag); however, little is known about their trafficking and function. In this study, we hypothesized that MP cells, naive to TCR stimulation, constitute a transient population that traffics to tissues during development. Using mutant and transgenic animals with a monospecific TCR, we discovered increased numbers of MP CD8+ T cells circulating in nonimmunized Cxcr3−/− and Cxcl10−/− mice compared with wild-type animals. Phenotypic differences included decreased numbers of preimmune MP Ag-specific T cells in the skin and thymus and a distinct pattern of activation upon TCR engagement. Our results show for the first time, to our knowledge, an important role for CXCR3 and CXCL10 in the tissue distribution of preimmune MP cells.

Footnotes

  • This work was supported by the Agence National de la Recherche (ANR-14-CE14-0030 PriCelAge to C.A. and M.L.A.), the Ligue contre le Cancer (to M.L.A.), the Fondation ARC pour la Recherche sur le Cancer (to M.L.A.), the European Union Seventh Framework Programme Marie Curie Action (PCIG11-GA-2012-3221170 to M.A.I.), and the French Government’s Invest in the Future Program, managed by the Agence Nationale de la Recherche (LabEx Immuno-Onco [to C.A., R.B.d.S., M.A.I., and M.L.A.] and LabEx Milieu Interieur [postdoctoral fellowship to C.A. and M.L.A.]). C.A. received a Ph.D. fellowship from Institut National du Cancer (Soutien à la Recherche Formation en Recherche Translationelle), and R.B.d.S. was the recipient of a Pasteur-Roux postdoctoral fellowship from the Institut Pasteur.

  • Abbreviations used in this article:

    MP
    memory phenotype
    SP
    single positive
    TRM
    tissue-resident memory
    WT
    wild-type.
  • Received May 3, 2017.
  • Accepted October 30, 2017.

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