In Kidney International Reports (Vol. 9, Issue 8), a study of 100 kidney transplant recipients with varying degrees of BKPyV reactivation found that biopsy-proven BKPyV-associated nephropathy (BKPyVAN) leads to a profound loss of BKPyV-specific T‑cell proliferation, cytokine secretion and cytotoxicity. This impairment is tied to over‑expression of inhibitory receptors such as PD‑1, CTLA‑4, TIM‑3 and TIGIT and is worsened when donor and recipient HLA class II differences are minimaldoaj.org. Conversely, when class II HLA mismatches are greater, allogeneic CD4 T cells help rescue CD8 T‑cell responsesdoaj.org. These results suggest that leveraging allogeneic CD4 T‑cell help may preserve antiviral immunity and protect kidney grafts from BKPyVAN.

Researchers at Frontiers in Immunology developed a whole blood IFN‑γ release assay that detects JCV‑specific effector and effector memory T cells. The assay was positive in 84% of patients with active PML and only 3% of healthy donorsfrontiersin.org. Positivity rates increased in multiple sclerosis patients according to duration of natalizumab treatmentfrontiersin.org. This tool could help stratify PML risk and monitor the immune response against JCVfrontiersin.org.

A study in Transplantation followed 28 kidney transplant recipients with detectable BKPyV DNA in the blood after immunosuppression reduction. Thirteen patients quickly controlled the virus, whereas fifteen could not. Those failing to control BKPyV exhibited weaker T‑cell proliferation and cytokine secretion and had BKPyV‑specific T cells with an exhausted phenotype marked by high PD‑1 and TIM‑3 expressionjournals.lww.com. Importantly, combining anti‑PD‑1 and anti‑TIM‑3 antibodies restored antiviral CD8 T‑cell function ex vivojournals.lww.com, indicating that dual checkpoint blockade may become a therapeutic strategy against BKPyV nephropathy.