Research Article: Clinically Relevant Reactivation of Polyomavirus BK (BKPyV) in HLA-A02-Positive Renal Transplant Recipients Is Associated with Impaired Effector-Memory Differentiation of BKPyV-Specific CD8+ T Cells

Date Published: October 10, 2016

Publisher: Public Library of Science

Author(s): Michiel C. van Aalderen, Ester B. M. Remmerswaal, Kirstin M. Heutinck, Anja ten Brinke, Mariet C. W. Feltkamp, Neelke C. van der Weerd, Karlijn A. M. I. van der Pant, Frederike J. Bemelman, René A. W. van Lier, Ineke J. M. ten Berge, Hans H Hirsch.

http://doi.org/10.1371/journal.ppat.1005903

Abstract

Polyomavirus BK (BKPyV) frequently reactivates in immunosuppressed renal transplant recipients (RTRs) and may lead to graft loss due to BKPyV-induced interstitial nephritis (BKVN). Little is known on the differentiation of CD8+ T cells targeting BKPyV in RTRs. Here we investigated whether BKPyV-specific CD8+ T cell differentiation differs in RTRs with varying degrees of BKPyV reactivation and/or BKVN.

Partial Text

Polyomavirus BK (BKPyV) establishes a mode of latent infection in the vast majority of the general, immunocompetent population [1, 2]. However, in immunosuppressed renal transplant recipients (RTRs), BKPyV can escape the weakened immunological response leading to reactivation in up to 60% of the patients. In as much as 10% of these reactivations, the virus causes a severe interstitial nephritis (BKVN) in the allograft that is associated with graft loss [3, 4]. Until now, the only effective treatment option for BKPyV reactivation following renal transplantation involves tapering of the immunosuppressive drug therapy, allowing the patient’s immune system to recover and overcome the virus. However, this also increases the chance on allograft rejection [3, 4].

Here, we document that in renal transplant patients with high viral load and/or BKVN, the effector-memory differentiation of circulatory BKPyV VP1- and LTAG-specific CD8+ T cells is distinct from that in patients with low viral load. VP1-specific CD8+ T cells collected before transplantation started off with a TCM or early-differentiated TEM phenotype, whereas the LTAG-specific cells curiously primarily displayed a naïve-like phenotype. Nevertheless, following transplantation and viral reactivation in the Rlow patients, both VP1- and LTAG-specific populations differentiated into CD28− TEM cells, with LTAG-specific cells even acquiring the TEMRA state. In the Rhigh and BKVN patients, VP1- and LTAG-specific CD8+ T cells instead generally persisted in their TCM and CD28+CD27+ TEM differentiation state.

 

Source:

http://doi.org/10.1371/journal.ppat.1005903

 

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