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

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  = .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 CD 8 + T cells after transplantation, we compared the number of HLA ‐A2–restricted CMV ‐specific CD 8 + 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 CD 8 + T cells/million CD 8 + 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 CD 8 + T cells, likely because of frequent CMV replications within the graft.