title: Distinct populations of innate CD8+ T cells revealed in a CXCR3 reporter mouse.
abstract: 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.
authors: Department of Pathology, The Ohio State University Medical Center, Columbus, OH 43210, USA.
authors: Steve
authors: S
authors: Oghumu
authors: Ran
authors: R
authors: Dong
authors: Sanjay
authors: S
authors: Varikuti
authors: Todd
authors: T
authors: Shawler
authors: Thomas
authors: T
authors: Kampfrath
authors: Cesar A
authors: CA
authors: Terrazas
authors: Claudio
authors: C
authors: Lezama-Davila
authors: Brian M M
authors: BM
authors: Ahmer
authors: Caroline C
authors: CC
authors: Whitacre
authors: Sanjay
authors: S
authors: Rajagopalan
authors: Richard
authors: R
authors: Locksley
authors: Arlene H
authors: AH
authors: Sharpe
authors: Abhay R
authors: AR
authors: Satoskar
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000166:cytology* / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D002465:Cell Movement; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D018703:Founder Effect; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D007113:Immunity, Innate; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D018715:Microscopy, Video; D054388:Receptors, CCR / Q000235:genetics / Q000276:immunology; D054367:Receptors, CXCR3 / Q000235:genetics* / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D051017:Apoptosis Regulatory Proteins; C119309:CC chemokine receptor 9; C515188:Cxcr3 protein, mouse; D016207:Cytokines; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; C494192:Ly-6C antigen, mouse; D054388:Receptors, CCR; D054367:Receptors, CXCR3; D049452:Green Fluorescent Proteins