Contribution of CD4+ T cells to the early mechanisms of ischemia- reperfusion injury in a mouse model of acute renal failure

Abstract

Renal ischemia-reperfusion (IR) injury is the major cause of acute renal failure in native and transplanted kidneys. Mononuclear leukocytes have been reported in renal tissue as part of the innate and adaptive responses triggered by IR. We investigated the participation of CD4 + T lymphocytes in the pathogenesis of renal IR injury. Male mice (C57BL/6, 8 to 12 weeks old) were submitted to 45 min of ischemia by renal pedicle clamping followed by reperfusion. We evaluated the role of CD4 + T cells using a monoclonal depleting antibody against CD4 (GK1.5, 50 µ, ip), and class II-major histocompatibility complex molecule knockout mice. Both CD4-depleted groups showed a marked improvement in renal function compared to the ischemic group, despite the fact that GK1.5 mAb treatment promoted a profound CD4 depletion (to less than 5% compared to normal controls) only within the first 24 h after IR. CD4-depleted groups presented a significant improvement in 5-day survival (84 vs 80 vs 39%; antibody treated, knockout mice and non-depleted groups, respectively) and also a significant reduction in the tubular necrosis area with an early tubular regeneration pattern. The peak of CD4-positive cell infiltration occurred on day 2, coinciding with the high expression of ßC mRNA and increased urea levels. CD4 depletion did not alter the CD11b infiltrate or the IFN-γ and granzyme-B mRNA expression in renal tissue. These data indicate that a CD4 + subset of T lymphocytes may be implicated as key mediators of very early inflammatory responses after renal IR injury and that targeting CD4 + T lymphocytes may yield novel therapies.

Insights into the Role of Chemokines, Damage-Associated Molecular Patterns, and Lymphocyte-Derived Mediators from Computational Models of Trauma-Induced Inflammation

“…It is generally agreed that trauma suppresses CD4 + T-cell responses (54,83,124,159). For example, Th1-type immune responses have been shown to be reduced markedly following trauma in patients and in mouse injury models (42,73,104).…”

O contexto do transplante renal no Brasil e sua disparidade geográfica

“…This becomes even more important when recent studies have suggested that there are no patient and graft survival differences between kidney transplant recipients on steroids and azathioprine/tacrolimus or mycophenolate/tacrolimus regimens, pointing to azathioprine as a therapeutic option for selected patients ( Figure 12). 54 advances in the understanding of the molecular and cellular mechanisms involved in the ischemia and reperfusion injury, [55][56][57] and in human operational tolerance. 58 peRspectives Brazil has experimented advances in its social organization, which can be evidenced by an increased life expectation at birth (76 years for women and 69 years for men), 59 a decreased birth rate (reduced from 5.6 to 2.1 in the past 30 years), 60 reduced infant mortality rate, and reduced urban violence and number of violent deaths (from 13,257 in 1999 to 4,436, in 2007, in São Paulo).…”

Role of Ocimum Canum in Prevention of Reperfusion-Induced Renal Ischemia in Wistar Albino Rats

“…It was demonstrated that reactive oxygen species (ROS) and reactive nitrogen species (RNS) increase in the areas of ischemia and reperfusion, which are responsible for renal damage. Inflammation also plays an important role in the pathogenesis of renal I/R injury, through leukocyte activation and expression of adhesion molecules and cytokines [1][2][3][4][5][6] . Free radicals and pro-inflammatory cytokines can damage cellular membrane and subcellular structures, which contain large amounts of phospholipids and protein, resulting in lipid peroxidation and sequentially structural and IJBAR (2012) 03(07) www.ssjournals.com metabolic alterations, leading to cell apoptosis and necrosis.…”