BK virus-specific T-cell immune reconstitution after allogeneic hematopoietic cell transplantation
| Autor: | Ritz, Jerome, Marty, Francisco M., Soiffer, Robert J., Antin, Joseph H., Koreth, John, Ho, Vincent T., Cutler, Corey S., Armand, Philippe, Alyea, Edwin P., Romee, Rizwan, Gooptu, Mahasweta, Nikiforow, Sarah, Lacerda, João, Soares, Maria Vieira, Forcade, Edouard, Avigan, Jason I., Woolley, Ann E., Kim, Haesook T., Cheng, Matthew P., Espada, Eduardo |
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| Přispěvatelé: | Repositório da Universidade de Lisboa |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Popis: | © 2020 by The American Society of Hematology 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-γ+ 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. This work was supported by a Collaborative Research Grant from the Harvard Medical School–Portugal Program in Translational Research HMSP-ICT/0001/201, National Institutes of Health, National Cancer Institute grants CA183559, CA183560, and CA229092, and the Pasquarello Tissue Bank in Hematologic Malignancies. E.E. is a PhD candidate at Universidade de Lisboa, and this work is submitted in partial fulfillment of the requirement for a PhD and was supported by a grant for medical fellows enrolled in a PhD program (Subsídios aos Internos Doutorandos–SINTD) from Fundação para a Ciência e Tecnologia, number SFRH/SINTD/135312/2017 |
| Databáze: | OpenAIRE |
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