Inflammatory activation and recovering BKV-specific immunity correlate with self-limited BKV replication after renal transplantation

Transpl Int. 2014 Mar;27(3):290-301. doi: 10.1111/tri.12251. Epub 2013 Dec 17.


As BKV-associated nephropathy has emerged as an important cause of allograft failure, it has been of major importance to find immune mechanisms suitable to identify kidney transplant recipients (KTRs) at increased risk of BKV replication. We monitored 29 KTRs with seven measurements during the first year post-transplantation. BKV-specific T cells directed to 5 BKV proteins were analyzed in an interferon-γ ELISPOT assay. BKV-specific antibodies were measured using an ELISA. The extent of immunosuppression and inflammatory activation were quantified by measures of immune function including lymphocyte subpopulations, IP-10, and adhesion molecule serum levels. All 5 BKV-specific T cells increased significantly from diagnosis to resolution of BKV replication (P<0.001). While antistructural T cells were significantly higher in KTRs with BKV replication (P<0.05), no differences were observed for antismall t- and large T-antigen-directed T cells (P>0.05). Interestingly, 65% of KTRs without BKV replication showed transient appearance of antismall t- and large T-antigen-directed T cells. Although no significant differences were observed for T-cell subpopulations and adhesion molecules, IP-10 levels increased significantly during BKV replication (P<0.05). Assessment of BKV-specific T cells identifies recovering BKV-specific immunity in KTRs with BKV replication and suggests their protective ability in KTRs without BKV replication. Increases in IP-10 levels stress the importance of infiltrating inflammatory leukocytes in the regulation of BKV replication and point to inflammatory activation in the pathogenesis of BKV replication.

Keywords: BKV replication; ELISPOT; IP-10; Renal transplantation; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood
  • Antigens, Viral
  • BK Virus / immunology
  • BK Virus / pathogenicity*
  • BK Virus / physiology
  • Chemokine CXCL10 / blood
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 / blood
  • Interferon-gamma / biosynthesis
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Nephritis / etiology
  • Nephritis / immunology
  • Polyomavirus Infections / etiology
  • Polyomavirus Infections / immunology
  • Prospective Studies
  • Risk Factors
  • T-Lymphocytes / immunology
  • Transplantation Immunology
  • Tumor Virus Infections / etiology
  • Tumor Virus Infections / immunology
  • Vascular Cell Adhesion Molecule-1 / blood
  • Virus Activation / immunology
  • Virus Replication / immunology


  • Antibodies, Viral
  • Antigens, Viral
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma