Distinct Populations of Innate CD8+ T Cells Revealed in a CXCR3 Reporter Mouse
Autor: | Sanjay Varikuti, Caroline C. Whitacre, Arlene H. Sharpe, Ran Dong, Steve Oghumu, Todd Shawler, Abhay R. Satoskar, Brian M. M. Ahmer, Cesar Terrazas, Claudio M. Lezama-Davila, Sanjay Rajagopalan, Thomas Kampfrath, Richard M. Locksley |
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Rok vydání: | 2013 |
Předmět: |
Male
Gene Expression CD8-Positive T-Lymphocytes CXCR3 Transgenic Green fluorescent protein Mice Interleukin 21 Genes Reporter Cell Movement immune system diseases Receptors Antigens Ly Innate 2.1 Biological and endogenous factors Immunology and Allergy Cytotoxic T cell Aetiology skin and connective tissue diseases Microscopy Microscopy Video biology Video hemic and immune systems Founder Effect Cytokines Receptors CXCR3 Green Fluorescent Proteins Immunology Mice Transgenic Article Receptors CCR stomatognathic system Antigen Immunity Animals Cell Lineage Antigens Reporter Cell Proliferation CCR Molecular biology Immunity Innate Interleukin-2 Receptor beta Subunit stomatognathic diseases Ly Genes Granzyme biology.protein Apoptosis Regulatory Proteins CD8 |
Zdroj: | Journal of immunology (Baltimore, Md. : 1950), vol 190, iss 5 |
ISSN: | 1550-6606 0022-1767 |
DOI: | 10.4049/jimmunol.1201170 |
Popis: | CXCR3, expressed mainly on activated T and NK cells, is implicated in a host of immunological conditions and can contribute either to disease resolution or pathology. We report the generation and characterization of a novel CXCR3 internal ribosome entry site bicistronic enhanced GFP reporter (CIBER) mouse in which enhanced GFP expression correlates with surface levels of CXCR3. Using CIBER mice, we identified two distinct populations of innate CD8+ T cells based on constitutive expression of CXCR3. We demonstrate that CXCR3+ innate CD8+ T cells preferentially express higher levels of Ly6C and CD122, but lower levels of CCR9 compared with CXCR3− innate CD8+ T cells. Furthermore, we show that CXCR3+ innate CD8+ T cells express higher transcript levels of antiapoptotic but lower levels of proapoptotic factors, respond more robustly to IL-2 and IL-15, and produce significantly more IFN-γ and granzyme B. Interestingly, CXCR3+ innate CD8+ T cells do not respond to IL-12 or IL-18 alone, but produce significant amounts of IFN-γ on stimulation with a combination of these cytokines. Taken together, these findings demonstrate that CXCR3+ and CXCR3− innate CD8+ T cells are phenotypically and functionally distinct. These newly generated CIBER mice provide a novel tool for studying the role of CXCR3 and CXCR3-expressing cells in vivo. |
Databáze: | OpenAIRE |
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