Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation.
Human cytomegalovirus (HCMV) remains an important cause of morbidity after allotransplantation, causing a range of direct effects including hepatitis, pneumonitis, enteritis and retinitis. A dominant risk factor for HCMV disease is high level viral replication in blood but it remains unexplained why only a subset of patients develop such diseases. In this detailed study of 25 renal transplant recipients, we show that functional impairment of HCMV specific CD8 T cells in the production of interferon gamma was associated with a 14-fold increased risk of progression to high level replication. The CD8 T-cell impairment persisted during the period of high level replication and was more prominent in patients above 40 years of age (odds ratio = 1.37, p = 0.01) and was also evident in dialysis patients. Threshold levels of functional impairment were associated with an increased risk of future HCMV replication and there was a direct relationship between the functional capacity of HCMV ppUL83 CD8 T cells and HCMV load (R(2)= 0.83). These results help to explain why a subset of seropositive individuals develop HCMV replication and are at risk of end-organ disease and may facilitate the early identification of individuals who would benefit from targeted anti-HCMV therapy after renal transplantation.
Mattes
F M
FM
Department of Infection, Royal Free and University College Medical School (Hampstead campus) and Royal Free Hampstead NHS Trust, London, UK.
Vargas
A
A
Kopycinski
J
J
Hainsworth
E G
EG
Sweny
P
P
Nebbia
G
G
Bazeos
A
A
Lowdell
M
M
Klenerman
P
P
Phillips
R E
RE
Griffiths
P D
PD
Emery
V C
VC
D000998:Antiviral Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000627:therapeutic use; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D016133:Polymerase Chain Reaction; D011183:Postoperative Complications / Q000453:epidemiology / Q000821:virology; D011446:Prospective Studies; D014779:Virus Replication
D000998:Antiviral Agents; D004279:DNA, Viral; D007371:Interferon-gamma; D015774:Ganciclovir