Polyomavirus BK VP1-Speficifc CD8+ T Cells Circulating in Healthy Adults Are Polyfunctional Early Differentiated Memory Cells.

Abstract

Background: Polyomavirus BK (BKV) is a very common virus that establishes a mode of latent infection in the urogenital tract. In kidney transplant recipients it is known to cause severe interstitial nephritis that may lead to graft loss. Unfortunately, no specific and effective antiviral therapy is available. For the development of BKV-specific T-cell therapies, it is crucial to understand the normal BKV-specific immunological response occurring in healthy individuals. Methods/materials: Using tetramers loaded with immunodominant VP1 epitopes and stimulation assays we were able to determine phenotype and function of circulating HLA-A02-resticted VP1-specific CD8+ T-cells in 5 of 25 HLA-A02-positive healthy adults. Results: VP1-specific CD8+ T-cells were found to be predominantly early differentiated CD45RA-CCR7-CD27+ memory cells that highly express CXCR3 and CD49d. They were polyfunctional since they were able to rapidly secrete interleukin-2, interferon-γ, tumour necrosis factor-α, MIP-1-β and CD107 upon antigenic recall. Conclusion: BKV VP1-specific CD8+ T-cells circulating in healthy individuals are early differentiated polyfunctional memory cells.