Cytomegalovirus-specific CD8+ T cells do not develop in all renal transplant patients at risk of virus infection.
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.
Christmas
Stephen E
SE
Division of Immunology, School of Infection and Host Defence, University of Liverpool, Liverpool, UK. sechris@liv.ac.uk
Halliday
Deborah
D
Lawton
Nichola
N
Wang
Haiyi
H
Abdalla
Ibrahim
I
Masters
James
J
Hassan
Rebecca L
RL
Hart
Ian J
IJ
Khan
Naeem
N
Smith
Jane
J
Hammad
Abdul
A
Bakran
Ali
A
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
D000998:Antiviral Agents; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C065418:cytomegalovirus matrix protein 65kDa