Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: IL-21 exhibits a wide range of immunomodulatory functions in the organism, regulating immune cells such as B cells and T cells. In this study, a mice transplantation model was constructed. B cells, Regulatory B cells (B10), CD4+ T cells, CD4+CD25+Foxp3+ Treg cells as well as related cytokines in different Th cell subgroups were observed dynamically. The regulation of IL-21 on Th cellular immunity was further elucidated, providing an updated basis for exploring the mechanism of acute rejection after renal transplantation.
*Methods: The kidney transplantation model was constructed using C57BL/6 mice (6-9 weeks, female) divided into 2 groups. 10 mice in each group were injected with 10ml 100 ng/ml IL-21 through caudal vein 1h before, 2d, 4d, and 6d after surgery (IL-21 group), and the control group received equivalent saline (control group).All peripheral blood and spleen tissue suspension were collected 7 days after operation and added to 1640 culture medium containing fetal bovine serum (FBS). The FACS Canto II flow cytometry was utilized to detect the number of B cells, B10 cells, CD4+ T cells and CD4+CD25+Foxp3+ Treg cells. The contents of IL-2, IFN-γ, TNF-α, IL-4, IL-10, IL-6, IL-17a and IL-21 in peripheral blood, transplanted kidney and spleen tissue suspension were detected by Elisa method. The allograft tissues of in each group were histopathological detected, based on the Banff grading system.
*Results: IL-21 induced proliferation and differentiation of various cell subgroups. In peripheral blood, CD4+T cells, Treg cells, B cells and proportion of B10 cells in B cells were higher in IL-21 group with a significant difference (9.05 ± 0.60 vs. 5.82 ± 0.52, 5.95 ± 0.69 vs. 2.14 ± 0.85, 36.98 ± 4.90 vs. 30.68 ± 3.89, 0.75±0.07 vs. 0.24±0.02, p<0.05). In the spleen tissue suspension, B cells and B10 cells were observed significantly lower (32.93 ± 1.56 vs. 42.60 ± 5.09, 1.58 ± 0.37 vs. 2.50 ± 0.59, p<0.05).
IL-21 promoted immune deviation of Th2 to Th1 cells. The cytokines related to Th cell subgroup in the IL-21 group demonstrated a trend of Th2 to Th1 immune deviation. Among them, Th1 specific cytokines IFN-γ and TNF-α in transplanted kidney significantly elevated in peripheral blood (120.89 ± 10.75 vs. 58.6 ± 7.01, 41.57 ± 3.63 vs. 29.58 ± 2.64, p<0.05). In the spleen, Th2 specific cytokines IL-10 and IL-6 decreased (18.23 ± 2.88 vs. 28.33 ± 2.61, 23.68 ± 2.33 vs. 29.54 ± 3.96, p<0.05) while IL-21 increased (4.42 ± 1.06 vs. 1.70 ± 0.48, p<0.05). TNF-α, IL-6 and IL-21 in peripheral blood elevated (45.25 ± 1.32 vs. 39.31 ± 2.20, 60.72 ± 10.53 vs. 39.83 ± 1.88, p<0.05) and IL-21 decreased (6.09 ± 0.54 vs. 10.05 ± 0.66, p<0.05).
IL-21 induced acute rejection of the transplanted kidney. Among control group that survived 7 days post operation (n=7), two (28.6%) showed no rejection reaction, one (14.3%) with mild interstitial inflammation, four (57.2%) with moderate or severe interstitial inflammation. One of them (14.3%) showed peripheral tubular capillary inflammation (PTC) of grade 1 and four (57.1%) of grade 2. Meanwhile, among the IL-21 group (n=9), all (100.0%) showed moderate to severe interstitial inflammation. Two (22.2%) with PTC grade 2, and three (33.3%) with PTC grade 3.
*Conclusions: IL-21 can promote differentiation and proliferation of spleen cells and induce immune deviation of Th2 to Th1 cells, aggravating acute rejection of the transplanted kidney.
To cite this abstract in AMA style:Deng H, Wang R, Shen J, Chen J. IL-21 Induces the Transformation of Th Cell Subsets in Acute Rejection after Kidney Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/il-21-induces-the-transformation-of-th-cell-subsets-in-acute-rejection-after-kidney-transplantation/. Accessed July 23, 2019.
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