BACKGROUND: In Th (T helper) 1/Th2 balance in response to signals given during donor antigen presentation, induction of allograft prolongation is more often related to Th2-type than with Th1-type immunity. Here, we examined the effect of interleukin (IL)-33, a novel member of the IL-1 family, on cardiac allograft survival in mice. METHODS: Mice heterotopic cardiac transplants were performed with sequential recipient sacrifice at anticipated time points to examine the immunoregulatory action of IL-33 in recipient mice. RESULTS: In vitro Th1-polarized CD4 T cells did not express ST2L; however, most CD4 T cells became ST2L on repeated stimulation under Th2-polarizing conditions. Similarly, we found that IL-33 was able to enhance the expression of Th2-associated cytokines (IL-5 and IL-13) but not interferon (IFN)-gamma. Treatment of recipient mice with IL-33 results in the improvement of allograft survival (more than 20 days) when compared with phosphate-buffered saline- or glutathione S-transferase-treated groups (all less than 9 days). Intracellular cytokine staining in CD4 splenocytes confirmed an increase in the percentage of IL-4 cells and a decrease in the percentage of IFN-gamma cells in IL-33 treated mice. In addition, IL-33 significantly enhanced the gene expression of Th2-type cytokines IL-4 and IL-5 but suppressed the Th1-type cytokine IFN-gamma mRNA levels in both allograft and recipient spleen. CONCLUSION: These data demonstrate that IL-33 serves as a potent inducer of Th2 immune response and can markedly contribute to the prolongation of cardiac allograft survival.
BACKGROUND: In Th (T helper) 1/Th2 balance in response to signals given during donor antigen presentation, induction of allograft prolongation is more often related to Th2-type than with Th1-type immunity. Here, we examined the effect of interleukin (IL)-33, a novel member of the IL-1 family, on cardiac allograft survival in mice. METHODS:Mice heterotopic cardiac transplants were performed with sequential recipient sacrifice at anticipated time points to examine the immunoregulatory action of IL-33 in recipient mice. RESULTS: In vitro Th1-polarized CD4 T cells did not express ST2L; however, most CD4 T cells became ST2L on repeated stimulation under Th2-polarizing conditions. Similarly, we found that IL-33 was able to enhance the expression of Th2-associated cytokines (IL-5 and IL-13) but not interferon (IFN)-gamma. Treatment of recipient mice with IL-33 results in the improvement of allograft survival (more than 20 days) when compared with phosphate-buffered saline- or glutathione S-transferase-treated groups (all less than 9 days). Intracellular cytokine staining in CD4 splenocytes confirmed an increase in the percentage of IL-4 cells and a decrease in the percentage of IFN-gamma cells in IL-33 treated mice. In addition, IL-33 significantly enhanced the gene expression of Th2-type cytokines IL-4 and IL-5 but suppressed the Th1-type cytokine IFN-gamma mRNA levels in both allograft and recipient spleen. CONCLUSION: These data demonstrate that IL-33 serves as a potent inducer of Th2 immune response and can markedly contribute to the prolongation of cardiac allograft survival.
Authors: Pavel Kopach; Virginia Lockatell; Edward M Pickering; Ronald E Haskell; Richard D Anderson; Jeffrey D Hasday; Nevins W Todd; Irina G Luzina; Sergei P Atamas Journal: J Biol Chem Date: 2014-03-11 Impact factor: 5.157
Authors: Tengfang Li; Zhongqiang Zhang; Joe G Bartolacci; Gaelen K Dwyer; Quan Liu; Lisa R Mathews; Murugesan Velayutham; Anna S Roessing; Yoojin C Lee; Helong Dai; Sruti Shiva; Martin H Oberbarnscheidt; Jenna L Dziki; Steven J Mullet; Stacy G Wendell; James D Wilkinson; Steven A Webber; Michelle Wood-Trageser; Simon C Watkins; Anthony J Demetris; George S Hussey; Stephen F Badylak; Hēth R Turnquist Journal: J Clin Invest Date: 2020-10-01 Impact factor: 14.808
Authors: Benjamin M Matta; Jeremy M Lott; Lisa R Mathews; Quan Liu; Brian R Rosborough; Bruce R Blazar; Hēth R Turnquist Journal: J Immunol Date: 2014-09-12 Impact factor: 5.422