活体肝移植中与移植物排斥相关的CD4 T细胞亚群改变
Alterations in CD4 T-cell Subsets in Living Donor Liver Transplantation Associated With Graft Rejection.
作者信息
Vagadiya Ankur, Sehgal Rashi, Trehanpati Nirupma, Pamecha Viniyendra
机构信息
Department of Hepato Pancreato Biliary and Liver Transplant Surgery, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, India.
Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, India.
出版信息
J Clin Exp Hepatol. 2024 Sep-Oct;14(5):101428. doi: 10.1016/j.jceh.2024.101428. Epub 2024 Apr 16.
BACKGROUND AND OBJECTIVES
Regulatory T-cells (Tregs) play a key role in immune homeostasis after organ transplantation. However, the role of CD4 T cell subsets in early acute rejection is still not well understood. Therefore, our aim was to determine changes in CD4 T-cell subsets in living donor liver transplantation (LDLT).
METHODS
LDLT patients were assessed for T-cell subsets, Tregs frequencies and their functionality by flow-cytometry at peri- and post-transplant in the span of 1 year.
RESULTS
33 patients were followed up and 11 (33%) patients have developed early acute cellular rejection (ACR). At peri-transplant time point, MFI of Foxp3 Tregs was significantly increased compared to HC ( = 0.04). However, CD4CD25Foxp3/CD127 Tregs numbers and IL-10, IL-17 and TGF-β secreting functional Tregs were significantly decreased at 3 months compared to peri-transplant ( = 0.003). But in patients with rejection, CD4CD25FOXP3 and CD4CD25CD127 Tregs were significantly decreased at day 3 compared to no rejection group ( = 0.048). Patients with rejection also showed significantly decreased numbers of IL-17 and TGF-β secreting CD4CD25FOXP3 Tregs at peri-transplant time ( = 0.04, = 0.03) compared to no rejection. Further, rejection group showed decreased terminally differentiated effector memory (TEMRA) at peri-transplant and day 7 ( = 0.048 and = 0.01). Additionally, CD4 central memory (CM) was decreased at peri-transplant ( = 0.05), 1 month ( = 0.04), and 3 to 6 month ( = 0.02).
INTERPRETATION AND CONCLUSION
Tregs frequencies were significantly decreased in peri-TX in rejection patients. Further, decreased frequencies of CD4 TEMRA and CD4 CM at day 7 and 1 month were associated with rejection.
背景与目的
调节性T细胞（Tregs）在器官移植后的免疫稳态中起关键作用。然而，CD4 T细胞亚群在早期急性排斥反应中的作用仍未完全明确。因此，我们的目的是确定活体肝移植（LDLT）中CD4 T细胞亚群的变化。
方法
对LDLT患者在移植前后1年内通过流式细胞术评估T细胞亚群、Tregs频率及其功能。
结果
33例患者接受随访，11例（33%）患者发生早期急性细胞排斥反应（ACR）。在移植时，与健康对照（HC）相比，Foxp3 Tregs的平均荧光强度（MFI）显著升高（P = 0.04）。然而，与移植时相比，3个月时CD4⁺CD25⁺Foxp3⁺/CD127⁻ Tregs数量以及分泌IL-10、IL-17和TGF-β的功能性Tregs显著减少（P = 0.003）。但在发生排斥反应的患者中，与无排斥反应组相比，术后第3天CD4⁺CD25⁺FOXP3⁺和CD4⁺CD25⁺CD127⁻ Tregs显著减少（P = 0.048）。与无排斥反应患者相比，发生排斥反应的患者在移植时分泌IL-17和TGF-β的CD4⁺CD25⁺FOXP3⁺ Tregs数量也显著减少（P = 0.04，P = 0.03）。此外，排斥反应组在移植时和第7天终末分化效应记忆（TEMRA）细胞减少（P = 0.048和P = 0.01）。另外，CD4⁺中央记忆（CM）细胞在移植时（P = 0.05）、1个月时（P = 0.04）以及3至6个月时（P = 0.02）减少。
解读与结论
发生排斥反应的患者在移植时Tregs频率显著降低。此外，第7天和1个月时CD4⁺TEMRA和CD4⁺CM细胞频率降低与排斥反应相关。
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