IL-10 producing T cells (Tr1) are important for the transplant tolerance induction. However, Tr1 can be induced in two methods: IL-27 or TGF-βplus IL-27. We still do not know which one is better for transplant tolerance induction. First, we generated foxp3-GFP IL-10-Thy1.1 mice, sorted Foxp3- naïve T cells, and differentiated into Tr1 by IL-27 OR TGF-βplus IL-27. We found no difference on IL-10 expression between the two groups. However, RNA-seq showed that Tr1 generated by IL-27 expressed more pathogenic genes, such as IL-23R, but less tolerant genes, such as prdm1, irf1, Tim-3, Batf. When co-cultured with effector T cells, we found that Tr1 generated by TGF-βplus IL-27 could better inhibit the T cell proliferation. Further, we adoptively transferred the Tr1 into allogeneic heart transplant mice (intravenously) to induce tolerance, and found that both Tr1 could prolong the graft survival, but the graft in TGF-βplus IL-27 group could survive longer than the other one, and the graft infiltrating T cells express less IFN-g, but more IL-10. At last, we found that the two kinds of Tr1 were much similar by RNA-seq when generated from IL-23R ko T cells, suggesting the function of Tr1 generated by TGF-βplus IL-27 may be dependent on IL-23R. In summary, the Tr1 generated by TGF-βplus IL-27 is better than that generated by IL-27 for transplant tolerance induction.

CITATION INFORMATION: Gu G, Hang H, Xia Q. Which Tr1 Is Better for Transplant Tolerance Induction: Comparing the Tr1 Generated by IL-27 or TGF-βplus IL-27. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress