Polyomavirus BK-specific cellular immune response to VP1 and large T-antigen in kidney transplant recipients

Am J Transplant. 2007 May;7(5):1131-9. doi: 10.1111/j.1600-6143.2007.01754.x. Epub 2007 Mar 12.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / immunology
  • Antigens, Viral / immunology
  • Antigens, Viral, Tumor / immunology*
  • BK Virus / immunology*
  • BK Virus / pathogenicity
  • Capsid Proteins / immunology*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Immunosuppression
  • Interferon-gamma / metabolism
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / pathology
  • Male
  • Middle Aged
  • Pilot Projects
  • Polyomavirus Infections / immunology
  • Polyomavirus Infections / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Tumor Virus Infections / immunology
  • Tumor Virus Infections / pathology
  • Viral Load
  • Virus Replication*

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Antigens, Viral, Tumor
  • Capsid Proteins
  • VP1 protein, polyomavirus
  • Interferon-gamma