BK virus–specific T-cell immune reconstitution after allogeneic hematopoietic cell transplantation

Abstract

Clinical disease caused by BK virus reactivation is a frequent complication of allogeneic hematopoietic cell transplantation (HCT). Because of the lack of effective antiviral agents, BK virus–specific T cells are emerging as a potential therapy for BK virus disease, but the immune response to BK virus after allogeneic HCT has not been well characterized. Our study describes reconstitution of BK virus–specific T-cell immunity in 77 adult patients after HCT. All patients had urinary symptoms, and urine was tested for BK virus replication; 33 patients were positive for BK virus (cases), and 44 were negative (controls). In BK virus cases, the median time to first positive test was 75 days (range, 2-511). BK virus cases had lower CD4 T-cell counts 3 to 9 months after transplant, but CD8 T-cell counts were similar in cases and controls. BK virus–specific T cells were identified by cytokine flow cytometry in cryopreserved samples collected prospectively. BK virus–specific CD4 T cells producing T helper 1 (Th1) cytokines recovered quickly after HCT. BK virus–specific T cells were detected more frequently in patients with BK virus reactivation at most time points, and CD4 T cells producing Th1 cytokines were more frequent than BK virus–specific cytolytic CD8 T cells. Early detection of interferon-g1 and cytolytic BK virus–specific CD4 T cells was associated with lower rates of hematuria among cases. Overall, our study describes recovery of BK virus–specific T cells after HCT and the distinct roles for BK virus–specific T cells in the development and resolution of clinical symptoms.