Polyomavirus BK-specific cellular immune response to VP1 and large T-antigen in kidney transplant recipients.
Polyomavirus BK (BKV) is the primary cause of polyomavirus-associated nephropathy (PVAN) in kidney transplant (KT) recipients. Using ELISpot assays, we compared the frequency of interferon-gamma (IFN-gamma) secreting peripheral blood mononuclear cells (PBMC) after stimulation with overlapping peptide pools covering BKV large T-antigen (LT) and VP1 capsid proteins (VP1). In 10 healthy donors, LT and VP1 responses were low with median 24 (range 15-95) and 25 (7-113) spot-forming units/10(6) PBMC (SFU), respectively. In 42 KT patients with current or recent plasma BKV loads, median LT and VP1 responses of 29 (0-524) and 114 (0-1432) SFU were detected, respectively. In KT patients with decreasing or past plasma BKV loads, significantly higher median BKV-specific IFN-gamma responses were detected compared to KT patients with increasing or persisting BKV loads [LT: 78 (8-524) vs. 22 (0-120) SFU, p=0.003; VP1: 285 (45-1432) vs. 53 (0-423) SFU, p=0.001, respectively]. VP1-specific IFN-gamma responses were higher and more likely to involve CD4(+) T cells, while CD8(+) T cells were more frequently directed against LT. Stimulation with JCV-specific VP1 and LT peptides indicated only low-level cross-recognition. The data suggest that control of BKV replication is correlated with differentiated expansion of BKV-specific cellular immune responses.
Binggeli
S
S
Transplantation Virology, Institute for Medical Microbiology, University of Basel, Basel, Switzerland.
Egli
A
A
Schaub
S
S
Binet
I
I
Mayr
M
M
Steiger
J
J
Hirsch
H H
HH
D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D000957:Antigens, Viral, Tumor / Q000276:immunology*; D001739:BK Virus / Q000276:immunology* / Q000472:pathogenicity; D036022:Capsid Proteins / Q000276:immunology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D027601:Polyomavirus Infections / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014412:Tumor Virus Infections / Q000276:immunology / Q000473:pathology; D019562:Viral Load; D014779:Virus Replication
D000914:Antibodies, Viral; D000956:Antigens, Viral; D000957:Antigens, Viral, Tumor; D036022:Capsid Proteins; C062481:VP1 protein, polyomavirus; D007371:Interferon-gamma