*Purpose: Previous studies have shown that receptor tyrosine kinase Axl, primarily expressed on dendritic cells and some tissue-specific macrophage population, is required for T cells priming and induction of adaptive immunity. In the present study, we investigated whether Axl-deficient mice, when used as kidney allograft recipients, demonstrate impaired anti-donor T cell immunity.

*Methods: Bilaterally nephrectomized C57BL/6 mice that were (Axl-sufficient and Axl-deficient) were transplanted with fully-mismatched BALB/c kidneys. On day -1, prior to the transplantation, 2.5×10⁵ donor-reactive TCR75 CD4 T cells labeled with cell-proliferation indicator dye v450 were adoptively transferred to the recipients. These recipients were sacrificed on day 3 post-transplant for the assessment of anti-donor T cells response in renal allografts and spleens using flow cytometry.

*Results: We observed that the total numbers of alloreactive TCR75 CD4 T cells in renal allografts were significantly lower in Axl-deficient recipients in comparison to Axl-sufficient transplant recipients. In contrast, proliferation of TCR75 CD4 T cells by v450 dilution in the kidney allografts was not different between the two groups, suggesting that either trafficking or survival, but not proliferation, of the TCR75 cells in the kidney allograft was deterred by recipient Axl deficiency. Similar to TCR75 CD4 T cells, CD8 T cell infiltration to the kidney allografts was also significantly reduced in Axl-deficient recipients. Interestingly, such a difference was not observed outside the kidney allografts such as in the spleen, nor was it observed in the number of total CD4 T cells in the allografts, suggesting a role of Axl in mediating allo-specific T cell trafficking or survival in the allografts.

*Conclusions: Axl deficiency may impair recruitment and/or survival of alloreactive CD4 and CD8 T cells in kidney allografts following transplantation. Thus, therapeutic targeting of Axl in kidney transplantation may be clinically beneficial.

« Back to 2020 American Transplant Congress