Objective: To explore the effect of Bat3 on T cells and its function in transplant tolerance induction

Methods

We generated Bat3^flox/flox CD4-Cre + mice, sorted WT and Bat3cko naïve T cells and differentiated them into different T cell subsets in vitro. In vivo, we generated heart transplant models between WT and Bat3cko mice, checked the graft survival and the T cell function in the allograft. Further, the RNA-seq was performed betwwen WT and Bat3cko graft infiltrating T cells. We further checked the memory precursor T cells in the early, middle and late stage during LCMV Armstrong infection; at last we tested the relationship between Bat3 and mTOR complex by Western Blot and co-IP.

Results

Bat3cko T cell could express more IFN-γ, Tim-3 and IL-10, but less IL-2 and TNF-α than the WT controls during in vitro differentiation. No differences of IL-17 and Foxp3 expression were detected between WT and Bat3cko T cells. In the heart transplant model, the graft could survive longer in Bat3cko mice, and ex vivo analysis showed that Bat3cko T cells in the allograft expressed less IFN-γ, but more Tim-3 and IL-10 than cells in the WT mice. In the LCMV Armstrong infection model, there were much less virus-specific T cells and memory precursor T cells in Bat3cko mice;. The co-IP experiments showed Bat3 could bind to Rictor, and then regulate the function of mTORC2 complex and downstream molecules.

Conclusion

Bat3 could bind to Rictor and regulate the mTORC2 function. Loss of Bat3 could inhibit the T cell function and induce transplant tolerance.

CITATION INFORMATION: Gu G, Hang H, Xia Q. Loss of Bat3 Could Promote Transplant Tolerance by Regulating CD4 ⁺ T Cells Function. Am J Transplant. 2017;17 (suppl 3).

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