Chronic infection and cancer are associated with suppressed T cell responses in the presence of cognate antigen. Recent work identified memory-like CXCR5(+) TCF1(+) CD8(+) T cells that sustain T... Show moreChronic infection and cancer are associated with suppressed T cell responses in the presence of cognate antigen. Recent work identified memory-like CXCR5(+) TCF1(+) CD8(+) T cells that sustain T cell responses during persistent infection and proliferate upon anti-PD1 treatment. Approaches to expand these cells are sought. We show that blockade of interferon type 1 (IFN-I) receptor leads to CXCR5(+) CD8(+) T cell expansion in an IL-27- and STAT1-dependent manner. IFNAR1 blockade promoted accelerated cell division and retention of TCF1 in virus-specific CD8(+) T cells. We found that CD8(+) T cell-intrinsic IL-27 signaling safeguards the ability of TCF1(hi) cells to maintain proliferation and avoid terminal differentiation or programmed cell death. Mechanistically, IL-27 endowed rapidly dividing cells with IRF1, a transcription factor that was required for sustained division in a cell-intrinsic manner. These findings reveal that IL-27 opposes IFN-I to uncouple effector differentiation from cell division and suggest that IL-27 signaling could be exploited to augment self-renewing T cells in chronic infections and cancer. Show less
Bellini, E.; Barreira, .; Frusciante, N.; Hu, B.; Peirone, S.; Raveri, M.; ... ; Vernizzi, F. 2018
The combination/fusion of quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS)/optical coherence tomography (OCT) depends to a great extend on the co-registration of X-ray... Show moreThe combination/fusion of quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS)/optical coherence tomography (OCT) depends to a great extend on the co-registration of X-ray angiography (XA) and IVUS/OCT. In this work a new and robust three-dimensional (3D) segmentation and registration approach is presented and validated. The approach starts with standard QCA of the vessel of interest in the two angiographic views (either biplane or two monoplane views). Next, the vessel of interest is reconstructed in 3D and registered with the corresponding IVUS/OCT pullback series by a distance mapping algorithm. The accuracy of the registration was retrospectively evaluated on 12 silicone phantoms with coronary stents implanted, and on 24 patients who underwent both coronary angiography and IVUS examinations of the left anterior descending artery. Stent borders or sidebranches were used as markers for the validation. While the most proximal marker was set as the baseline position for the distance mapping algorithm, the subsequent markers were used to evaluate the registration error. The correlation between the registration error and the distance from the evaluated marker to the baseline position was analyzed. The XA-IVUS registration error for the 12 phantoms was 0.03 +/- A 0.32 mm (P = 0.75). One OCT pullback series was excluded from the phantom study, since it did not cover the distal stent border. The XA-OCT registration error for the remaining 11 phantoms was 0.05 +/- A 0.25 mm (P = 0.49). For the in vivo validation, two patients were excluded due to insufficient image quality for the analysis. In total 78 sidebranches were identified from the remaining 22 patients and the registration error was evaluated on 56 markers. The registration error was 0.03 +/- A 0.45 mm (P = 0.67). The error was not correlated to the distance between the evaluated marker and the baseline position (P = 0.73). In conclusion, the new XA-IVUS/OCT co-registration approach is a straightforward and reliable solution to combine X-ray angiography and IVUS/OCT imaging for the assessment of the extent of coronary artery disease. It provides the interventional cardiologist with detailed information about vessel size and plaque size at every position along the vessel of interest, making this a suitable tool during the actual intervention. Show less
The combination/fusion of quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS)/optical coherence tomography (OCT) depends to a great extend on the co-registration of X-ray... Show moreThe combination/fusion of quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS)/optical coherence tomography (OCT) depends to a great extend on the co-registration of X-ray angiography (XA) and IVUS/OCT. In this work a new and robust three-dimensional (3D) segmentation and registration approach is presented and validated. The approach starts with standard QCA of the vessel of interest in the two angiographic views (either biplane or two monoplane views). Next, the vessel of interest is reconstructed in 3D and registered with the corresponding IVUS/OCT pullback series by a distance mapping algorithm. The accuracy of the registration was retrospectively evaluated on 12 silicone phantoms with coronary stents implanted, and on 24 patients who underwent both coronary angiography and IVUS examinations of the left anterior descending artery. Stent borders or sidebranches were used as markers for the validation. While the most proximal marker was set as the baseline position for the distance mapping algorithm, the subsequent markers were used to evaluate the registration error. The correlation between the registration error and the distance from the evaluated marker to the baseline position was analyzed. The XA-IVUS registration error for the 12 phantoms was 0.03 ± 0.32 mm (P = 0.75). One OCT pullback series was excluded from the phantom study, since it did not cover the distal stent border. The XA-OCT registration error for the remaining 11 phantoms was 0.05 ± 0.25 mm (P = 0.49). For the in vivo validation, two patients were excluded due to insufficient image quality for the analysis. In total 78 sidebranches were identified from the remaining 22 patients and the registration error was evaluated on 56 markers. The registration error was 0.03 ± 0.45 mm (P = 0.67). The error was not correlated to the distance between the evaluated marker and the baseline position (P = 0.73). In conclusion, the new XA-IVUS/OCT co-registration approach is a straightforward and reliable solution to combine X-ray angiography and IVUS/OCT imaging for the assessment of the extent of coronary artery disease. It provides the interventional cardiologist with detailed information about vessel size and plaque size at every position along the vessel of interest, making this a suitable tool during the actual intervention. Show less
Background: Accurate on-line assessments of vessel dimensions are of utmost importance for selecting the appropriate stent size in coronary interventions. Recently a new three-dimensional... Show moreBackground: Accurate on-line assessments of vessel dimensions are of utmost importance for selecting the appropriate stent size in coronary interventions. Recently a new three-dimensional quantitative coronary angiography (3D QCA) analytical software package was developed to accurately assess the vessel dimensions for the planning and guidance of such coronary interventions. This study aimed to validate the 3D QCA software package for assessing arterial segment length by comparing with intravascular ultrasound (IVUS). In addition, the difference in the two measurements from 3D QCA and IVUS for curved segments was studied. Methods: A retrospective study including 20 patients undergoing both coronary angiography and IVUS examinations of the left coronary artery was set up for the validation. The same vessel segments of interest between proximal and distal markers were identified and measured on both angiographic and IVUS images, by the 3D QCA software and by a quantitative IVUS software package, respectively. In addition, the curvature of each of the segments of interest was assessed and the correlation between the accumulated curvature of the segment and the difference in segment lengths measured from the two imaging modalities was analyzed. Results: 37 vessel segments of interest were identified from both angiographic and IVUS images. The 3D QCA segment length was slightly longer than the IVUS segment length (15.42 +/- 6.02 mm vs. 15.12 +/- 5.81 mm, P = 0.040). The linear correlation of the two measurements was: 3D QCA Length = -0.09 + 1.03 x IVUS Length (r(2) = 0.98, P < 0.001). Bland-Altman plot showed that the difference in the two measurements was not correlated with the average of the two measurements (P = 0.141), but with the accumulated curvature of the segment (P = 0.015). After refining the difference by the correlation, the average difference of the two measurements decreased from 0.30 +/- 0.86 mm (P = 0.040) to 0.00 +/- 0.78 mm (P = 0.977). Conclusions: The 3D QCA software package can accurately assess the actual arterial segment length. The difference in segment lengths measured from 3D CICA and IVUS was correlated with the accumulated curvature of the segment. (C) 2010 Wiley-Liss, Inc. Show less
