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Polyomavirus BK‐Specific Cellular Immune Response to VP1 and Large T‐Antigen in Kidney Transplant Recipients
Author(s) -
Binggeli S.,
Egli A.,
Schaub S.,
Binet I.,
Mayr M.,
Steiger J.,
Hirsch H. H.
Publication year - 2007
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2007.01754.x
Subject(s) - elispot , bk virus , immune system , peripheral blood mononuclear cell , nephropathy , immunology , antigen , medicine , cd8 , virology , polyomavirus infections , kidney , kidney transplantation , biology , endocrinology , biochemistry , diabetes mellitus , in vitro
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‐γ (IFN‐γ) 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‐γ 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‐γ 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.