3 years ago

CMV-infected kidney grafts drive the expansion of blood-borne CMV-specific T cells restricted by shared class I HLA molecules via presentation on donor cells

Christophe Baron, Sally Al-Hajj, Gilles Thibault, Philippe Gatault, Matthias Büchler, Johan Noble, Catherine Forconi, Eloi Chevallier, Elodie Miquelestorena-Standley, Marie Piollet, Roxane Lemoine, Catherine Gaudy-Graffin, Jean Michel Halimi
We aimed to determine the role of cytomegalovirus (CMV)-infected donor cells in the development of a CMV-specific immune response in kidney transplant recipients. We assessed the CMV pp65-specific immune response by using interferon-ɣ ELISPOT and dextramers in peripheral blood mononuclear cells from 115 recipients (D+R- 31, D+R+ 44, D-R+ 40) late after transplantation (mean 59±42 months). Receiving a kidney from a D+ donor resulted in a higher number of IFN-ɣ-producing anti-CMV T-cells (p=0.004). This effect disappeared with the absence of shared HLA class I specificities between donors and recipients (p=0.430). To confirm the role of donor cells in stimulating the expansion of newly developed CMV-specific CD8+ T cells after transplantation, we compared the number of HLA-A2–restricted CMV-specific CD8+ T cells in primo-infected recipients who received an HLA-A2 or non–HLA-A2 graft. The median of anti-CMV pp65 T cells restricted by HLA-A2 was very low for patients who received a non–HLA-A2 graft versus an HLA-A2 graft (300 [0-14638] vs 17972 [222-85594] anti-CMV pp65 CD8+ T cells/million CD8+ T cells, p=0.001). This adds new evidence that CMV-infected kidney donor cells present CMV peptides and drive an inflation of memory CMV-specific CD8+ T cells, likely because of frequent CMV replications within the graft. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/ajt.14672

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