{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:36:28Z","timestamp":1789677388470,"version":"4.0.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>More evidence have shown that the combination of immune and inflammatory mechanism was critical in diabetic nephropathy (DN). However, the relationship between CD4+ T cells and the development of DN is still unclear. Therefore, this study will focus on this issue from the perspective of clinicopathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From September 2019 to December 2022, a total of 112 adult patients with DN were enrolled in the study. According to the density of CD4+ T cell infiltration based on immunostaining, the patients were divided into high-CD4 group (56 patients) and low-CD4 group (56 patients). Another 25 diabetic patients with minimal change disease (non-diabetic nephropathy, NDN) was reviewed as control group in clinical and molecular analysis. The clinical parameters, morphological features, and molecular characteristics were compared. The predictive value of CD4+ T cells for DN prognosis was also investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>DN patients in the high-CD4 group suffered from higher proteinuria and lower estimated glomerular filtration rate (eGFR) level than those in the low-CD4 group and NDN patients. Renal biopsy in the high-CD4 group presented with more severe glomerular lesions, higher density of interstitial inflammation, and more severe tubular atrophy\/interstitial fibrosis than in the low-CD4 group. Multivariate logistic analysis indicated that the density of CD4+ T cell infiltration could independently predict the severity of tubular atrophy\/interstitial fibrosis. In addition, more severe mitochondrial damage of renal tubular epithelial cells and a more obvious expression of Bcl6, IL-6, STAT3, and TGF\u03b21 were observed in DN patients of the high-CD4 group, indicating the possible mechanism of CD4+ T cells involving the progression of DN. Multivariate Cox regression analysis revealed that a higher intensity of interstitial CD4+ T cell deposition remained as an independent predictor of the double endpoint with doubling of baseline serum creatinine or end-stage renal disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The high density of CD4+ T cell infiltration was associated with renal function decline and severity of renal lesions and predicted poor renal survival for DN patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1474377","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T06:24:32Z","timestamp":1732515872000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Higher density of CD4+ T cell infiltration predicts severe renal lesions and renal function decline in patients with diabetic 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