*Purpose: Allogeneic transplants elicit dynamic T cell responses that are modulated by positive and negative co-stimulatory receptors. We have investigated the impact of PD-1, a negative co-stimulatory receptors, on the rejection of MHC incompatible renal transplants in mice.

*Methods: A/J (H-2^a) kidneys were perfused with UW solution and subjected to a clinically relevant 4 hours of cold-ischemia prior to transplantation to bilaterally nephrectomized C57BL/6 (H-2^b) recipients. Recipients were injected intraperitoneally with 200 μg of IgG2a rat monoclonal to PD-L1 (clone 10F.9G2) or isotype control (clone LTF-2) antibody on days 3, 5 (Group 1) or 7, 9, 11 (Group 2). Daily urine samples were collected and mice in group 1 and 2 were sacrificed at 6 and 12 days, respectively. Allografted kidneys were excised for protein and histological analysis.

*Results: We found that T cells rapidly infiltrate A/J (H-2^a) kidneys transplanted to C57BL/6 (H-2^b) mice. The number of T cells peaked at 6 days and declined by day 14. The T cells primarily encircle tubules with moderate numbers infiltrating the tubular epithelium. Lipocalin 2 (Lcn2), a marker of tubular injury, also peaked at day 6 in the urine and then declined. Flow cytometry demonstrated that most of the T cells expressed PD-1 (>90% od CD8 and about 75% of CD4 cells) at day 6 after transplantation. Administration of blocking antibody to the PD-L1 ligand for PD-1 before day 6 increased the number of CD8⁺ and CD4⁺ T cells, upregulated expression of perforin and granzyme B, and exponentially increased urinary Lcn2. In contrast, blocking PD-1/PD-L1 interactions after day 6 resulted in a transient increase in urinary Lcn2.

*Conclusions: These data indicate that PD-1/PD-L1 interactions are most critical regulating acute T cell responses.

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