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

Am J Transplant. 2018 Aug;18(8):1904-1913. doi: 10.1111/ajt.14672. Epub 2018 Mar 3.


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 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.

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.

MeSH terms

  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cross-Sectional Studies
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • Female
  • Genes, MHC Class I / immunology*
  • Graft Rejection / etiology*
  • Humans
  • Kidney Transplantation / adverse effects*
  • Leukocytes, Mononuclear / immunology*
  • Male
  • Middle Aged
  • Peptide Fragments / immunology
  • Phosphoproteins / immunology
  • Retrospective Studies
  • T-Lymphocytes, Cytotoxic / immunology
  • Tissue Donors*
  • Viral Matrix Proteins / immunology


  • Antigens, Viral
  • Peptide Fragments
  • Phosphoproteins
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa