Generation and characterization of a CXCR3-EGFP bicistronic reporter (CIBER) mouse reveals phenotypically and functionally distinct populations of innate CD8+ T cells (44.9)

Abstract

Abstract The chemokine receptor CXCR3 is expressed mainly on activated T cells, NK cells and NKT cells. CXCR3 is implicated in a host of immunological conditions and it contributes either to disease resolution or pathology. Here, we report the generation and characterization of a novel CXCR3 IRES bicistronic EGFP reporter (CIBER) mouse in which EGFP expression correlates with surface levels of CXCR3. Using CIBER mice, we have identified two distinct populations of innate CD8+ T cells, one which constitutively express CXCR3 and the other which does not. We demonstrate that CXCR3+ innate CD8+ T cells preferentially express higher levels of Ly6C and CD122 but lower levels of CCR9 compared to CXCR3- innate CD8+ T cells. Furthermore, we show that CXCR3+ innate CD8+ T cells express high transcript levels of anti-apoptotic and low levels of pro-apoptotic co-stimulatory molecules, respond more robustly to IL-2 and IL-15, and produce significantly more IFN-γ and granzyme B as compared to CXCR3- innate CD8+ T cells. Interestingly, CXCR3+ innate CD8+ T cells do not respond to IL-12 or IL-18 alone, but produce significant amounts of IFN-γ upon 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. CIBER mice could be a novel tool for studying the role of CXCR3 and CXCR3-expressing cells in vivo during infectious, autoimmune and neoplastic diseases.