The human polyomavirus BK virus (BKV) establishes a latent and asymptomatic infection in the majority of the population. In immunocompromised individuals, the virus frequently (re)activates and may cause severe disease such as interstitial nephritis and hemorrhagic cystitis. Currently, the therapeutic options are limited to reconstitution of the antiviral immune response. T cells are particularly important for controlling this virus, and T cell therapies may provide a highly specific and effective mode of treatment. However, little is known about the phenotype and function of BKV-specific T cells in healthy individuals. Using tetrameric BKV peptide-HLA-A02 complexes, we determined the presence, phenotype, and functional characteristics of circulating BKV VP1-specific CD8 ؉ T cells in 5 healthy individuals. We show that these cells are present in low frequencies in the circulation and that they have a resting CD45RA ؊ CD27 ؉ memory and predominantly CCR7 ؊ CD127 ؉ KLRG1 ؉ CD49d hi CXCR3 hi T-bet int Eomesodermin lo phenotype. Furthermore, their direct cytotoxic capacity seems to be limited, since they do not readily express granzyme B and express only little granzyme K. We compared these cells to circulating CD8 ؉ T cells specific for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and influenza virus (Flu) in the same donors and show that BKV-specific T cells have a phenotype that is distinct from that of CMV-and EBV-specific T cells. Lastly, we show that BKV-specific T cells are polyfunctional since they are able to rapidly express interleukin-2 (IL-2), gamma interferon (IFN-␥), tumor necrosis factor ␣, and also, to a much lower extent, MIP-1 and CD107a.
In healthy individuals, the polyomavirus BK virus (BKV) establishes a latent, or "smoldering," but asymptomatic infection. However, in immunocompromised individuals, the virus frequently escapes the normal immunological surveillance to become systemically active, after which it may cause severe pathology. BKV elicits interstitial nephritis of the allograft in about 5% of kidney transplant recipients, making it an important cause of graft failure and graft loss. In up to 30% of hematopoietic stem cell transplant (HSCT) recipients, the virus induces hemorrhagic cystitis, thereby significantly contributing to morbidity and length of hospitalization (1).Currently, the main mode of therapy for patients suffering from BKV infection comprises reconstitution of the immunological antiviral response. In solid organ transplant recipients, this is achieved through tapering of the immunosuppressive medication. Unfortunately, this comes at the cost of increased allograft rejection, and in HSCT recipients this is an unattractive approach due to a considerable increase in the risk of graft-versus-host disease. So far, antiviral agents, such as cidofovir and leflunomide, have shown little effect on BKV replication in vivo (1). It is therefore crucial to develop new modes of therapy. In this regard, the normal T cell response was shown to be very important for keeping BKV at b...