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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2008
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| _version_ | 1826295943148863488 |
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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. |
| first_indexed | 2024-03-07T04:08:44Z |
| format | Journal article |
| id | oxford-uuid:c718a4dc-7ed0-440c-962b-0ba700e35308 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:08:44Z |
| publishDate | 2008 |
| record_format | dspace |
| 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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