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 |
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| Authors: | Philippe Gatault Sally Al‐Hajj Johan Noble Eloi Chevallier Marie Piollet Catherine Forconi Catherine Gaudy‐Graffin Gilles Thibault Elodie Miquelestorena‐Standley Jean‐Michel Halimi Matthias Büchler Roxane Lemoine Christophe Baron |
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| Affiliation: | 1. EA4245 T2I Transplantation Immunologie Inflammation, University of Tours, Tours, France;2. Service de Néphrologie et Immunologie Clinique, CHRU de Tours, Tours, France;3. Laboratory of Bacteriology and Virology Tours, CHRU de Tours, Tours, France;4. Laboratory of Immunology Tours, CHRU de Tours, Tours, France;5. Department of Pathology, CHRU de Tours, Tours, France |
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| Abstract: | 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‐? 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‐?‐producing anti‐CMV T cells (P = .004). This effect disappeared with the absence of shared HLA class I specificities between donors and recipients (P = .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 vs an HLA‐A2 graft (300 [0‐14638] vs. 17972 [222‐85594] anti‐CMV pp65 CD8+ T cells/million CD8+ T cells, P = .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. |
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| Keywords: | antigen presentation/recognition basic (laboratory) research/science complication: infectious infection and infectious agents – viral: Cytomegalovirus (CMV) infectious disease kidney transplantation/nephrology translational research/science |
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