Donor Ag-reactive CD4 and CD8 T cell production of IFN-γ is a principal effector mechanism promoting tissue injury during allograft rejection. The CXCR3-binding chemokines CXCL9 and CXCL10 recruit donor-reactive T cells to the allograft, but their role during the priming of donor-reactive T cells to effector function is unknown. Using a murine model of MHC-mismatched cardiac transplantation, we investigated the influence of CXCL9 and CXCL10 during donor-reactive T cell priming. In allograft recipient spleens, CXCL9 and CXCL10 were expressed as early as 24 h posttransplant and increased with similar kinetics, concurrently with CXCR3 expression on T cells. CXCL9, but not CXCL10, expression required NK cell production of IFN-γ. The absence of CXCL9 in donor allografts, recipients, or both significantly decreased the frequency of donor-reactive CD8 T cells producing IFN-γ and increased the frequency of donor-reactive CD8 T cells producing IL-17A. In contrast, the absence of CXCL10 increased the frequency of IFN-γ–producing CD8 T cells in a CXCL9-dependent manner. These data provide novel evidence that donor-reactive CD8 T cells use the CXCR3 chemokine axis as a costimulation pathway during priming to allografts where CXCL9 promotes the development of IFN-γ–producing CD8 T cells, and CXCL10 antagonizes this skewing.
Neutrophil activation to release granules containing proteases and other enzymes is a primary cause of tissue damage during ischemia/reperfusion injury. Because the contribution of specific granule enzymes to this injury remains poorly defined, the role of cathepsin G in renal ischemia/reperfusion injury was tested. Bilateral renal ischemia led to the expiration of 64% of wild-type mice within 4 days of reperfusion, whereas all cathepsin G-deficient mice survived. Serum creatinine increased to similar levels at 24 hours after reperfusion and then decreased to background in both groups of mice. Ischemic kidneys from both groups had similar levels of neutrophil infiltration and of CXCL1, CXCL2, and myeloperoxidase protein 9 hours after reperfusion, but at 24 hours, these acute inflammatory response components were decreased more than 50% in kidneys from cathepsin G-deficient versus wild-type mice. Ischemic kidneys from surviving wild-type mice had severe tubular necrosis and tubular cell apoptosis 24 hours after reperfusion with subsequent development of fibrosis 30 days later. In contrast, ischemic kidneys from cathepsin G-deficient mice had a 70% decrease in tubular cell apoptosis with little detectable collagen deposition. These data identify cathepsin G as a critical component sustaining neutrophil-mediated acute tissue pathology and subsequent fibrosis after renal ischemia/ reperfusion injury.
SUMMARYThe variability from year-to-year of the seasonal evolution in the southern hemisphere stratosphere over a period of 10 years, from 1980 to 1989, is investigated using the global geopotential height derived from the data from the Stratospheric Sounding Unit on board the TIROS-N NOAA satellites. As a measure of interannual variability, the variance of the zonal mean geostrophic wind over thc 10 years was calculated for each day. Although the major warming hardly occurs in the southern hemisphere stratosphere, large variances can he observed during the winter and spring. The maximum variances appear at low latitudes in late autumn, move towards mid latitudes in midwinter and remain near 6 0 3 in spring. The seasonal movement of the zonal mean westerly jet in the southern hemisphere stratosphere can be classified into two categories in terms of the location of the maximum westerlies at the 1 mb level in midwinter, namely HLJ (high-latitude-jet) years with maximum westerlies around 50'3, LLJ (low-latitude-jet) years with maximum westerlies around 40"s.During the late winter the core of the westerly jet moves polewards earlier in HLJ years than in LLJ years. In association with this earlier movement, the growth of the amplitudes of the planetary waves 1 and 2 during the period from winter to spring occurs earlier in HLJ years than in LLJ years. In autumn, however, the wave-1 amplitude, only for LLJ years, develops vigorously in the stratosphere and even also in the troposphere, before the seasonal movement of the zonal mean westerly jet branches off into the two categories. The appearances of HLJ and LLJ years occur in groups of a few years; this is quite different from the behaviour of the equatorial quasi-biennial oscillation.
(1) title of the article:Pediatric live kidney transplantation is safe and available for the patients with urological anomalies compared with as well as those with primary renal diseases respectively, in the urological or renal group. The acute rejection free and overall graft survival were similar in both groups. One patient in the urological group lost his graft while six patients in the renal group lost their grafts. Thus, the post-transplant clinical outcome of pediatric transplantation in patients with urological anomalies is comparable to that of recipients with primary renal disease. Appropriate urinary tract reconstruction and management is essential to reduce the risk of graft dysfunction due to urinary problems.
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