Programmed death-1 expression in liver transplant recipients as a prognostic indicator of cytomegalovirus disease |
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Authors: | La Rosa Corinna Krishnan Aparna Longmate Jeff Martinez Joy Manchanda Pooja Lacey Simon F Limaye Ajit P Diamond Don J |
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Affiliation: | Laboratory of Vaccine Research, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA. |
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Abstract: | Immunological parameters that distinguish solid-organ transplant (SOT) recipients at risk for life-threatening cytomegalovirus (CMV) disease are being actively pursued to aid posttransplant management. A candidate marker is programmed death (PD)-1 receptor, whose overexpression has been associated with disease progression during persistent viral infections. To determine whether levels of this negative regulator of T cell activity are altered in SOT recipients with symptoms of CMV disease, a comparative PD-1 expression analysis was done in healthy, CMV-positive individuals and in liver transplant recipients. PD-1 levels were measured among the total population of CD8(+) and CD8(+) T cells binding to CMV-specific major histocompatibility complex class I tetramers. Minimal PD-1 expression was found in the healthy, CMV-positive cohort, and symptomatic SOT recipients had significantly higher PD-1 levels. PD-1 up-regulation was significantly associated with incipient and overt CMV disease and with viremia. Our findings suggest that PD-1 could be developed as a prognostic tool to predict CMV disease and guide therapeutic interventions. |
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