title: Cytomegalovirus-specific CD8+ T cells do not develop in all renal transplant patients at risk of virus infection.
abstract: Cytomegalovirus (CMV) is an important pathogen in immunosuppressed renal transplant patients. At greatest risk are CMV IgG seronegative recipients (R-) of kidneys from CMV IgG seropositive donors (D+), although not all develop CMV disease. The aims of the study were to determine whether D+/R- patients who do or do not go on to develop CMV disease differ in their CD8+ T cell responses to CMV. Responses to the immunodominant NLVPMVATV peptide from the CMV structural protein pp65 in HLA-A2+ renal transplant patients were quantified using HLA tetramers/pentamers. Most D+/R+ patients had detectable tetramer+ cells while most D-/R- patients did not. Around 50% of D+/R- patients had some CD8+ tetramer+ cells and there was a strong correlation between % tetramer+ cells and the occurrence of a CMV infection post-transplantation (P<0.005). 18/41 (44%) of CMV negative patients receiving a kidney from a CMV+ donor failed to develop a detectable CMV infection, or significant numbers of tetramer+ cells. There was no relationship between CMV infection and acute cellular rejection. There was a tendency for patients who were given pre-emptive antiviral therapy to have lower levels of tetramer+ cells but this was not statistically significant. Hence the results show that CMV- patients receiving a kidney from a CMV+ donor do not inevitably acquire CMV infection. Those without CMV disease did not show any T cell response while most patients with detectable CMV developed specific CD8+ T cells.
authors.affiliation: Division of Immunology, School of Infection and Host Defence, University of Liverpool, Liverpool, UK. sechris@liv.ac.uk
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Christmas
authors.forename: Deborah
authors.initials: D
authors.lastname: Halliday
authors.forename: Nichola
authors.initials: N
authors.lastname: Lawton
authors.forename: Haiyi
authors.initials: H
authors.lastname: Wang
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Abdalla
authors.forename: James
authors.initials: J
authors.lastname: Masters
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hassan
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Hart
authors.forename: Naeem
authors.initials: N
authors.lastname: Khan
authors.forename: Jane
authors.initials: J
authors.lastname: Smith
authors.forename: Abdul
authors.initials: A
authors.lastname: Hammad
authors.forename: Ali
authors.initials: A
authors.lastname: Bakran
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000821:virology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology; D012189:Retrospective Studies; D013997:Time Factors; D019737:Transplants / Q000821:virology; D014763:Viral Matrix Proteins / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C065418:cytomegalovirus matrix protein 65kDa