Abstract：
:Continuous antigen stimulation during chronic infection or malignancy can promote functional T cell silencing, a phenomenon called T cell exhaustion. The prevalence and impact of T cell exhaustion following organ transplantation, another immune stimulus with persistently high antigen load, are unknown. Here, we characterized serially collected peripheral blood mononuclear cells from 26 kidney transplant recipients using time-of-flight mass cytometry (CyTOF) to define distinct subsets of circulating exhausted T cells and their relationship to induction therapy and allograft function. We observed an increase in specific subsets of CD4+ and CD8+ exhausted T cells from pre-transplant to 6-months post-transplant, with greater increases in participants given anti-thymocyte globulin induction than in participants who received no induction or non-depleting induction. The percentages of exhausted T cells at 6 months correlated inversely with adenosine triphosphate (ATP) production (a surrogate of T cell function) and with allograft interstitial fibrosis. Guided by the CyTOF data, we delineated a PD-1+CD57- phenotype for CD4+ and CD8+ exhausted T cells, and confirmed that these cells have limited capacity for cytokine secretion and ATP production. In an independent cohort of 50 kidney transplant recipients, we confirmed the predicted increase of PD-1+CD57- exhausted T cells after lymphocyte-depleting induction therapy and its direct correlation with better allograft function. Our findings suggest that monitoring T cell exhaustion can be useful for post-transplant risk assessment and support the need to develop and test strategies aimed at augmenting T cell exhaustion following kidney transplantation.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Fribourg M,Anderson L,Fischman C,Cantarelli C,Perin L,La Manna G,Rahman A,Burrell BE,Heeger PS,Cravedi Pdoi
10.1016/j.kint.2019.01.040subject
Has Abstractpub_date
2019-08-01 00:00:00pages
436-449issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(19)30192-9journal_volume
96pub_type
杂志文章abstract：INTRODUCTION:Transforming growth factor-beta (TGF-beta) is known to play a pivotal role in the regulation of extracellular matrix (ECM) accumulation. Since diabetic nephropathy (DMN) is characterized by basement membrane thickening and mesangial expansion, control of ECM deposition is believed to be important in the pa...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2003.00919.x
更新日期：2003-05-01 00:00:00
abstract：BACKGROUND:Heparins are currently the anticoagulants of choice in long-term hemodialysis (HD). Because of their shortcomings, including the increasing incidence of heparin-induced thrombocytopenia (HIT II), alternative anticoagulation is necessary. The study objectives were to provide safe and effective HD by investiga...
journal_title：Kidney international
pub_type： 临床试验,杂志文章
doi：10.1111/j.1523-1755.2004.00433.x
更新日期：2004-02-01 00:00:00
abstract：:Atherogenic lipoproteins and reactive oxygen species stimulate renin release from isolated juxtaglomerular (JG) cells. Here we assessed whether stimulation of renin release is mediated by formation of superoxide anion (O2-), and whether the effects of oxidized lipoproteins, like in many other biological systems, can b...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1997.30
更新日期：1997-01-01 00:00:00
abstract：:The initiation of peritonitis is accompanied by a massive increase in intraperitoneal levels of IL-6. The source of this cytokine and the mechanism by which its levels are increased so dramatically are unknown. We examined the mechanism of IL-6 secretion by HPMC exposed to the milicu present in the peritoneal cavity d...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1996.430
更新日期：1996-10-01 00:00:00
abstract：:Kidney disease is associated with increased cardiovascular morbidity, but underlying mechanisms are poorly understood. We tested the hypothesis that chronic renal insufficiency impairs angioadaptation in a rat model of hindlimb ischemia. Twenty male Sprague-Dawley rats (8 weeks old) underwent subtotal nephrectomy (5/6...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.5000448
更新日期：2006-06-01 00:00:00
abstract：BACKGROUND:Long-term graft function is the result of multiple parameters, including both immune and non-immune components, which have a beneficial or detrimental potential. Among these, despite its frequency and theoretical interest (expression of "danger signals" in the graft itself), the effects of acute graft pyelon...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2002.00323.x
更新日期：2002-05-01 00:00:00
abstract：:Hemodynamic studies were performed at two levels of dietary sodium intake (10 mmoles/day and 100 mmoles/day for 14 days) in a group of patients (with retained kidneys) on chronic hemodialysis. Plasma renin activity and aldosterone, plasma, and extracellular fluid (ECF) volumes were measured while the patient were at r...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1977.114
更新日期：1977-10-01 00:00:00
abstract：:Monocyte and macrophage markers are among the most highly overexpressed genes in cpk mouse kidneys with severely progressive renal cystic disease. We show here that one of these markers, CD14, is abnormally transcribed, activated and shed in cystic kidneys. However, these abnormalities were not associated with an incr...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2010.175
更新日期：2010-09-01 00:00:00
abstract：:We evaluated the contribution of intrarenal factors in the increased renal accumulation of bovine serum albumin (BSA) in chronic serum sickness (CSS). Renal transplantation was used to study 125I BSA uptake (single and paired label techniques) in normal and CSS kidneys exposed to the same immunologic milieu. In CSS, t...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1986.244
更新日期：1986-11-01 00:00:00
abstract：:Gain-of-function variants in CFB encoding factor B (FB), a component of the alternative pathway C3 convertase, have been reported in a minority of patients with aHUS and result in massive C3 activation. Zhang et al. describe the functional characterization of a novel FB variant (p.Ser367Arg) that they identified in 2 ...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1016/j.kint.2020.06.026
更新日期：2020-11-01 00:00:00
abstract：:We have sought to determine the mechanisms driving fluid secretion by the cystic epithelium in autosomal dominant polycystic kidney disease (ADPKD). We have performed in vitro experiments on intact cysts dissected from discarded ADPKD kidneys, on monolayers of cells cultured from the cystic epithelium and on microcyst...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1038/ki.1996.230
更新日期：1996-06-01 00:00:00
abstract：:We present a new hypothesis to explain the development of salt-dependent hypertension in humans. We propose that hypertension has two phases: an early phase in which elevations in blood pressure (BP) are mainly episodic and are mediated by a hyperactive sympathetic nervous or renin-angiotensin system, and a second pha...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1038/ki.1997.442
更新日期：1997-11-01 00:00:00
abstract：BACKGROUND:The tissue renin-angiotensin system (RAS) may modulate the structural and functional changes that occur in the diabetic kidney. METHODS:Hypertensive transgenic (mREN-2)27 rat (TGR) that exhibit increased tissue renin expression were administered streptozotocin (STZ, diabetic) or citrate buffer (non-diabetic...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1998.00019.x
更新日期：1998-08-01 00:00:00
abstract：:Murine double minute (MDM)-2, an E3 ubiquitin ligase, promotes cancer cell survival and growth, by degrading the cell cycle regulator p53. Antagonism of MDM2 by the small-molecule cis-imidazoline nutlin analogs is under current study for cancer therapy. To test whether MDM2 also promotes regenerative cell growth, we d...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2011.482
更新日期：2012-06-01 00:00:00
abstract：BACKGROUND:Since the cloning of the gene for autosomal dominant polycystic kidney disease type 2 (PKD2), approximately 40 different mutations of that gene have been reported to be associated with the disease. The relationship between the PKD2 genotype and phenotype, however, remains unclear. METHODS:Detailed clinical ...
journal_title：Kidney international
pub_type： 杂志文章,多中心研究
doi：10.1046/j.1523-1755.2000.00989.x
更新日期：2000-04-01 00:00:00
abstract：:Acid (H+) retention appears to contribute to progressive decline in glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD), including some patients without metabolic acidosis. Identification of patients with H+ retention but without metabolic acidosis could facilitate targeted alkali therapy; h...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2018.11.033
更新日期：2019-05-01 00:00:00
abstract：:To define the pattern of recovery from postischemic acute renal failure (ARF), we performed clearance and micropuncture studies at intervals of 1, 2, 4, and 8 weeks following 60 min of complete unilateral renal artery occlusion in the rat. At 1 week, the inulin clearance (CIn) of the postischemic kidney was less than ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1979.112
更新日期：1979-08-01 00:00:00
abstract：:Obesity has been suggested to have a detrimental impact on kidney structure and function, leading to focal glomerulosclerosis and hypertension. It is also associated with hyperleptinemia and elevated renal sympathetic nerve activity. Prenatal undernutrition promotes postnatal obesity, hypertension, and an altered rena...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.5002276
更新日期：2007-08-01 00:00:00
abstract：:Diabetic nephropathy shows a higher incidence in male subjects, which may in part be owing to genetic factors. The angiotensin II type 2 receptor (AT2), present in the renal glomerulus, may oppose the deleterious effects of the type I receptor (AT1) through vasodilatation and growth inhibition. We determined whether t...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.5000348
更新日期：2006-05-01 00:00:00
abstract：:Osteopontin (OPN) is a secreted acidic glycoprotein that has potent monocyte chemoattractant and adhesive properties. Up-regulation of tubular OPN expression is thought to promote interstitial macrophage infiltration in experimental nephritis; however, the role of OPN in glomerular lesions, particularly crescent forma...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1998.00748.x
更新日期：1998-01-01 00:00:00
abstract：BACKGROUND:Tacrolimus has a narrow therapeutic window, and bioavailability is known to vary considerably between renal transplant recipients. Most centers still rely on measurement of trough levels, but there are conflicting reports on the correlation between tacrolimus trough levels and systemic exposure, as measured ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1111/j.1523-1755.2005.00352.x
更新日期：2005-06-01 00:00:00
abstract：:Many subjects nowadays present with end-stage renal failure and its attendant cardiovascular complications without known prior renal damage. In this report we review the evidence available to strongly suggest that the present practice of secondary prevention in those with known prior renal disease should be extended t...
journal_title：Kidney international
pub_type： 杂志文章,评审
doi：10.1111/j.1523-1755.2004.66001.x
更新日期：2004-12-01 00:00:00
abstract：BACKGROUND:Elevated glucose levels and glomerular hypertension (Pgc) are considered to contribute to the elaboration of matrix protein by mesangial cells (MCs) in diabetic glomeruli. MCs grown in 30 mM of glucose produce excessive matrix protein, as do MCs exposed to cyclic strain, and the combination of the two exacer...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1999.00743.x
更新日期：1999-11-01 00:00:00
abstract：:Renal involvement in von Hippel-Lindau (VHL) disease has emerged as the most prevalent cause of death in this hereditary disorder. In a group of 43 VHL patients (23 unrelated families) with renal lesions we examined whether severity of renal disease is affected by parental inheritance and VHL subtype (1, without pheoc...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1996.395
更新日期：1996-09-01 00:00:00
abstract：BACKGROUND:Estradiol suppresses the synthesis of type I collagen by murine mesangial cells. However, neither the alpha 1(I) nor the alpha 2(I) collagen gene contains an estrogen-response element. Because estradiol modulates the transcription of several genes that lack an estrogen-response element but contain a regulato...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.1999.00376.x
更新日期：1999-04-01 00:00:00
abstract：:IgA nephropathy (IgAN) is the most prevalent primary chronic glomerular disease for which no safe disease-specific therapies currently exist. IgAN is an autoimmune disease involving the production of autoantigenic, aberrantly O-glycosylated IgA1 and ensuing deposition of nephritogenic immune complexes in the kidney. A...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2019.01.031
更新日期：2019-07-01 00:00:00
abstract：:Chronic kidney disease (CKD) promotes development of cardiac abnormalities and is highly prevalent in patients with heart failure, particularly in those with preserved ejection fraction. CKD is associated with endothelial dysfunction, however, whether CKD can induce impairment of endothelium-to-cardiomyocyte crosstalk...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2020.12.013
更新日期：2020-12-22 00:00:00
abstract：:Kallistatin is a serine protease inhibitor with anti-inflammatory, anti-angiogenic, and anti-oxidative properties. Since oxidative stress plays a critical role in the pathogenesis of diabetic nephropathy, we studied the effect and mechanisms of action of kallistatin superinduction. Using ultrasound-microbubble-mediate...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2015.331
更新日期：2016-02-01 00:00:00
abstract：:Renal toxicity, possibly due to vasoconstriction and vascular injury, is the most relevant side-effect of chronic cyclosporine (CsA) therapy given to prevent graft rejection. In kidney transplant recipients each oral dose of CsA is invariably followed by a transient reduction in renal plasma flow (RPF) and glomerular ...
journal_title：Kidney international
pub_type： 临床试验,杂志文章
doi：10.1038/ki.1993.101
更新日期：1993-03-01 00:00:00
abstract：BACKGROUND:It is known that inhibition of cyclooxygenase (COX) impairs the renal actions of loop diuretics. Recently, we found that cyclosporine A (CsA) inhibits renal COX-2 expression. Therefore, we examined the interferences of CsA with the renal actions of loop diuretics. METHOD:We investigated the renal effects of...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1111/j.1523-1755.2004.00627.x
更新日期：2004-06-01 00:00:00
