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...

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Main Authors: Mattes, F, Vargas, A, Kopycinski, J, Hainsworth, E, Sweny, P, Nebbia, G, Bazeos, A, Lowdell, M, Klenerman, P, Phillips, R, Griffiths, P, Emery, VC
Formato: Journal article
Idioma:English
Publicado em: 2008
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author Mattes, F
Vargas, A
Kopycinski, J
Hainsworth, E
Sweny, P
Nebbia, G
Bazeos, A
Lowdell, M
Klenerman, P
Phillips, R
Griffiths, P
Emery, VC
author_facet Mattes, F
Vargas, A
Kopycinski, J
Hainsworth, E
Sweny, P
Nebbia, G
Bazeos, A
Lowdell, M
Klenerman, P
Phillips, R
Griffiths, P
Emery, VC
author_sort Mattes, F
collection OXFORD
description 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.
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spelling oxford-uuid:c718a4dc-7ed0-440c-962b-0ba700e353082022-03-27T06:42:40ZFunctional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c718a4dc-7ed0-440c-962b-0ba700e35308EnglishSymplectic Elements at Oxford2008Mattes, FVargas, AKopycinski, JHainsworth, ESweny, PNebbia, GBazeos, ALowdell, MKlenerman, PPhillips, RGriffiths, PEmery, VCHuman 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.
spellingShingle Mattes, F
Vargas, A
Kopycinski, J
Hainsworth, E
Sweny, P
Nebbia, G
Bazeos, A
Lowdell, M
Klenerman, P
Phillips, R
Griffiths, P
Emery, VC
Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation.
title Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation.
title_full Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation.
title_fullStr Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation.
title_full_unstemmed Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation.
title_short Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation.
title_sort functional impairment of cytomegalovirus specific cd8 t cells predicts high level replication after renal transplantation
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