BKV Clearance Time Correlates With Exhaustion State and T-Cell Receptor Repertoire Shape of BKV-Specific T-Cells in Renal Transplant Patients

Abstract

Reactivation of the BK polyomavirus is known to lead to severe complications in kidney transplant patients. The current treatment strategy relies on decreasing the immunosuppression to allow the immune system to clear the virus. Recently, we demonstrated a clear association between the resolution of BKV reactivation and reconstitution of BKV-specific CD4 + T-cells. However, which factors determine the duration of viral infection clearance remains so far unclear. Here we apply a combination of in-depth multi-parametric flow cytometry and NGS-based CDR3 beta chain receptor repertoire analysis of BKV-specific T-cells to a cohort of 7 kidney transplant patients during the clinical course of BKV reactivation. This way we followed TCR repertoires at single clone levels and functional activity of BKV-specific T-cells during the resolution of BKV infection. The duration of BKV clearance did not depend on the number of peripheral blood BKV-specific T-cells nor on a few immunodominant BKV-specific T-cell clones. Rather, the T-cell receptor repertoire diversity and exhaustion status of BKV-specific T-cells affected the duration of viral clearance: high clonotype diversity and lack of PD1 and TIM3 exhaustion markers on BKV-specific T-cells was associated with short clearance time. Our data thus demonstrate how the diversity and the exhaustion state of the T-cells can determine the clinical course of BKV infection.

Immune monitoring facilitates the clinical decision in multifocal COVID-19 of a pancreas-kidney transplant patient

“…For allograft transplant patients, not only the high rate of these comorbidities and frequent contact with medical care, but also—and especially—immunosuppressive therapy can contribute to disease severity. Thus, a crucial role of T cell immunity for the viral clearance and vaccination response has been shown in previous studies 5‐7 . Because of immunosuppression, the quantity and the functionality of antiviral immunity can be impaired, whereas the impact of different immunosuppressive drugs can vary 6 .…”

Persistence of Antibody Responses to the SARS-CoV-2 in Dialysis Patients and Renal Transplant Recipients Recovered from COVID-19

“…The ongoing studies on the factors able to influence the achievement of adequate protection against SARS-CoV-2 infection and its persistence over time represent a hot topic of current research, with the goal of tailoring vaccination and immunotherapy protocols. Patients with impaired renal function commonly show a poorer humoral immune response with a less durable neutralizing function against infections [39,40]. To confirm this view, we evaluated a group of healthcare workers with no comorbidities or renal disease at six months following recovery from COVID-19.…”

BK Virus-Associated Nephropathy after Renal Transplantation

“…Meanwhile, an increase in BKV-specific T cells directed to BKV proteins (large T- and small t-antigen, and Vp1–3) was shown to predict successful control of BK viremia [ 93 , 96 , 97 ]. Recently, it was found that CD4+ T-cell exhaustion and the diversity of the antigen specific T-cell receptor repertoire affect the BKV clearance time [ 98 ].…”