CXCR3/CXCL10 Axis Shapes Tissue Distribution of Memory Phenotype CD8+ T Cells in Nonimmunized Mice

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 and 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.

Metformin enhances anti-mycobacterial responses by educating CD8+ T-cell immunometabolic circuits

“…The differential transcriptomic and phenotypic properties of metformin-educated CD8 + CXCR3 + T M cells suggest that these cells may represent another type of "innate CD8 + T-cell" 17 . The CXCR3/CXCL10 axis can shape the distribution of CD8 + T M cells in the tissues of non-immunized mice 53 and CXCR3-expressing innate CD8 + T M cells are known to express activation markers, respond to IL-2 and IL-15, and possess antibacterial effector function 54,55 . In addition, CXCR3 is required for the migration and establishment of CD8 + T CM cell population in the respiratory tract, where they protect against influenza A virus infection 29 .…”

The Role of CXCR3 and Its Chemokine Ligands in Skin Disease and Cancer

“…Immune effector cells such as Th1 CD4 T cells and CD8 T cells that express CXCR3 are frequently involved in inflammatory reactions and therefore it is not surprising that this receptor is often associated with inflammatory skin diseases. However, prior to inflammation, there is some evidence from CXCR3 −/− (and CXCL10 −/− ) mice that memory T cell accumulation within the skin may be dependent on the CXCR3/CXCL10 axis although development of tissue-resident memory CD8 T cells (Trm) in the epidermis appears to be independent of CXCR3 ( 62 , 63 ). CXCR3 most likely acts not as a skin-specific chemokine receptor but instead attracts immune cells to sites of interferon-mediated inflammation ( 64 ).…”

Metformin enhances anti-mycobacterial responses by educating immunometabolic circuits of CD8+T cells

“…The differential transcriptomic and phenotypic properties of metformin-educated CD8 + CXCR3 + TM cells suggest that these cells may represent another type of "innate CD8 + T cell sensor" 17 . The CXCR3/CXCL10 axis can shape the distribution of CD8 + TM cells in the tissues of non-immunized mice 53 and CXCR3-expressing innate CD8 + TM cells are known to express activation markers, respond to IL-2 and IL-15, and possess antibacterial effector function 54,55 . Additionally, CXCR3…”