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 micro, 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 betaC mRNA and increased urea levels. CD4 depletion did not alter the CD11b infiltrate or the IFN-gamma 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.
Highlights
Ischemia-reperfusion (IR) injury is inevitably associated with the retrieval, storage and transplantation of solid organs, especially with grafts from deceased donors [1]
GK1.5 monoclonal antibodies (mAb)-treated animals had a partial reconstitution of the CD4+ T cell population on days 1 and 2 after reperfusion, ranging from 26 to 38% of the values observed in matched controls
Two days after IR injury, G3 had a partial repopulation of CD4+ T cells compared to knockout mice, renal function did not differ between them
Summary
Ischemia-reperfusion (IR) injury is inevitably associated with the retrieval, storage and transplantation of solid organs, especially with grafts from deceased donors [1]. Many studies have shown that the inflammatory response induced by ischemia followed by reperfusion is largely responsible for the tissue damage, leading to functional organ failure [3,5,6,7]. This acute inflammatory response is characterized by the induction of a pro-inflammatory cytokine cascade [8], enhanced expression of adhesion molecules [5,8], up-regulation of the major histocompatibility complex (MHC) antigens, and cellular infiltration [5,6,7,8,9]. These data were not unanimously accepted and the role of neutrophils in tissue aggression is currently considered to be less important (9,1012)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Brazilian Journal of Medical and Biological Research
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
