M.C. van Aalderen, E.B.M. Remmerswaal, K.M. Heutinck, A. ten Brinke, K.A.M.I van Donselaar-van der Pant, N.C van der Weerd, F.J. Bemelman, M.C. Feltkamp, R.A.W. van Lier, I.J.M. ten Berge
Chair(s): dr. Ron W.F. de Bruin, Erasmus MC, Rotterdam
Thursday 10 march 2016
12:30 - 13:00h at Foyer
Parallel session: Postersessies XI - Opgesplitst in 3 tijdblokken en 3 categoriëen (klinisch, basaal, donatie)
Polyomavirus BK (BKV) causes severe interstitial nephritis (BKVN) in up to 10% of renal transplant recipients (RTRs), causing graft loss in a substantial number of them. Because T cell responses are important to viral control, we investigated the role of BKV-specific CD8+ T cell differentiation in the emergence of BKV reactivation and BKVN.
Using HLA A02-restricted tetramers loaded with immunodominant BKV VP1- and large T antigen (LTAG)-specific epitopes, we isolated BKV-specific CD8+ T cell populations from the blood of sixty-six HLA A02-positive individuals suffering to varying degrees from BKV reactivation and/or histologically proven BKVN. We investigated the differentiation of these BKV-specific CD8+ T cells in relation to disease severity, longitudinally in time after transplantation. For that, we measured the expression of differentiation markers like CD45RA and CD27, chemokine receptors, such as CCR7 and CXCR6, the serine proteases granzyme K and B, and the transcription factors, T-bet and eomesodermin.
As judged by these markers, BKV-specific CD8+ T cells from patients with strong reactivation (BKV-PCR >1*10e4 copies/ml) displayed a block in differentiation in comparison to patients who better succeeded in controlling the virus.
These findings indicate diminished differentiation of BKV-specific CD8+ T cells as a possible mechanism involved in the pathogenesis of severe BKV reactivation and BKVN.