Kidney Week

Abstract: TH-OR103

Kidney-Infiltrating CD4 and CD8 T Cells Differ in Functional Competence During Polyomavirus Infection

Session Information

• The Next Frontier in Kidney Transplantation: Omics, Gene Editing, and Precision Medicine
  October 22, 2026 | Location: Mile High Ballroom 4A, Convention Center
  Abstract Time: 05:00 PM - 05:10 PM

Category: Transplantation

• 2001 Transplantation: Basic

Authors

• Katz, Zoe, Penn State College of Medicine, Hershey, Pennsylvania, United States

Zoe Katz

• Lukacher, Aron, Penn State College of Medicine, Hershey, Pennsylvania, United States

Aron Lukacher, MD, PhD

Background

Donor-derived human BK polyomavirus (BKPyV) is responsible for PyV-associated nephropathy (PVAN), the major infectious cause of premature kidney allograft loss. Cytotoxic T cells control kidney BKPyV infection. BKPyV-specific CD8 T cells are dysfunctional in PVAN patients. Causes of CD8 dysfunction and BKPyV persistence remain unknown. We hypothesize that T cell dysfunction occurs early during BKPyV infection, resulting in viral persistence in the donor kidney. Given the strict species specificity of BKPyV, we analyzed virus-specific T cells in the kidneys of mice infected with mouse PyV (MuPyV).

Methods

C57BL/6 mice were systemically infected with MuPyV. Kidney T cell phenotype and function were analyzed by flow cytometry during acute and persistent infection. To characterize the impact of virus load on T cell responses, two novel MuPyV were generated. One has two LoxP sequences (A2-LoxP); the control virus has two nonsynonomous LoxP sequences (Lox2272 and Lox5171; A2-Lox25). Single-cycle replication assays, western blotting, and in vivo viral spread assays were used to compare recombinant viruses to wildtype. Rosa-Cre^ERT2 mice received tamoxifen IP from -1 to 3 days post infection (dpi). Mice were infected with A2-LoxP or A2-Lox25 SC at 0 dpi. Virus levels and T cell responses were analyzed 8 dpi.

Results

Spleen CD8 and CD4 T cells produce comparable levels of IFNγ and TNFa at 8 and 30 dpi following ex vivo peptide stimulation. Although kidney-infiltrating, virus-specific CD8 T cells are significantly attenuated in IFNγ, TNFa production and proliferative capacity, kidney CD4 T cells exhibit no defects. CD8 T cell dysfunction could not be attributed to expression of PD-1, Tim-3, Lag3, or CD94/NKG2A inhibitory receptors. Recombinant LoxP MuPyVs produce T antigens and replicate equally in vitro and in vivo compared to wildtype MuPyV. Reducing viral genomes lowered the magnitude of virus-specific CD8, but not CD4, T cell responses in the kidney and spleen.

Conclusion

These findings suggest kidney-specific CD8 T cells become dysfunctional early during MuPyV infection but CD4 T cells remain functionally intact. Previous studies in our lab implicate CD4, not CD8, T cell-mediated viral control during persistence. Ongoing work aims to understand how viral infection causes CD8 T cell dysfunction and how CD4 T cells control viral replication.

Funding

• Other NIH Support