BK Polyomavirus-Specific 9mer CD8 T Cell Responses Correlate With Clearance of BK Viremia in Kidney Transplant Recipients: First Report From the Swiss Transplant Cohort Study
| Autor: | C, Leboeuf, S, Wilk, R, Achermann, I, Binet, D, Golshayan, K, Hadaya, C, Hirzel, M, Hoffmann, U, Huynh-Do, M T, Koller, O, Manuel, N J, Mueller, T F, Mueller, S, Schaub, C, van Delden, F H, Weissbach, H H, Hirsch, Patrick, Yerly |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine T cell medicine.medical_treatment Viremia Human leukocyte antigen CD8-Positive T-Lymphocytes 030230 surgery Peripheral blood mononuclear cell Cohort Studies 03 medical and health sciences 0302 clinical medicine Humans Immunology and Allergy Medicine Cytotoxic T cell Pharmacology (medical) Aged Transplantation ddc:617 business.industry Immunosuppression Middle Aged medicine.disease Kidney Transplantation Virology 030104 developmental biology medicine.anatomical_structure BK Virus Case-Control Studies Immunology Female business CD8 |
| Zdroj: | American Journal of Transplantation, Vol. 17, No 10 (2017) pp. 2591-2600 |
| ISSN: | 1600-6135 |
| DOI: | 10.1111/ajt.14282 |
| Popis: | BK polyomavirus (BKPyV) causes premature kidney transplant (KT) failure in 1-15% of patients. Because antivirals are lacking, most programs screen for BKPyV-viremia and, if positive, reduce immunosuppression. To evaluate the relationship of viremia and BKPyV-specific immunity, we examined prospectively cryopreserved plasma and peripheral blood mononuclear cells at the time of transplantation (T0) and at 6 mo (T6) and 12 mo (T12) after transplant from 28 viremic KT patients and 68 nonviremic controls matched for the transplantation period. BKPyV IgG seroprevalence was comparable between cases (89.3%) and controls (91.2%; p = 0.8635), but cases had lower antibody levels (p = 0.022) at T0. Antibody levels increased at T6 and T12 but were not correlated with viremia clearance. BKPyV-specific T cell responses to pools of overlapping 15mers (15mer peptide pool [15mP]) or immunodominant CD8 9mers (9mer peptide pool [9mP]) from the early viral gene region were not different between cases and controls at T0; however, clearance of viremia was associated with stronger 9mP responses at T6 (p = 0.042) and T12 (p = 0.048), whereas 15mP responses were not informative (T6 p = 0.359; T12 p = 0.856). BKPyV-specific T cells could be expanded in vitro from all patients after transplant, permitting identification of 78 immunodominant 9mer epitopes including 50 new ones across different HLA class I. Thus, 9mP-responses may be a novel marker of reconstituting CD8 T cell function that warrants further study as a complement of plasma BKPyV loads for guiding immunosuppression reduction. |
| Databáze: | OpenAIRE |
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