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Am J Transplant. 2017 Aug;17(8):2045-2054. doi: 10.1111/ajt.14227. Epub 2017 Mar 13.

Cytomegalovirus-Responsive CD8+ T Cells Expand After Solid Organ Transplantation in the Absence of CMV Disease.

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Department of Medicine/Nephrology, Stanford University, Palo Alto, CA.
Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, PA.
Perelman School of Medicine, University of Pennsylvania, Renal Division, Philadelphia, PA.
Perelman School of Medicine, University of Pennsylvania, Cardiovascular Institute, Philadelphia, PA.
Stanford University, School of Medicine, Department of Pathology, Stanford, CA.
Perelman School of Medicine, University of Pennsylvania, Infectious Diseases Division, Philadelphia, PA.
Stanford University, School of Medicine, Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford, CA.
VA Palo Alto Health Care System, Palo Alto, CA.


Cytomegalovirus (CMV) is a major cause of morbidity and mortality in solid organ transplant recipients. Approximately 60% of adults are CMV seropositive, indicating previous exposure. Following resolution of the primary infection, CMV remains in a latent state. Reactivation is controlled by memory T cells in healthy individuals; transplant recipients have reduced memory T cell function due to chronic immunosuppressive therapies. In this study, CD8+ T cell responses to CMV polypeptides immediate-early-1 and pp65 were analyzed in 16 CMV-seropositive kidney and heart transplant recipients longitudinally pretransplantation and posttransplantation. All patients received standard of care maintenance immunosuppression, antiviral prophylaxis, and CMV viral load monitoring, with approximately half receiving T cell-depleting induction therapy. The frequency of CMV-responsive CD8+ T cells, defined by the production of effector molecules in response to CMV peptides, increased during the course of 1 year posttransplantation. The increase commenced after the completion of antiviral prophylaxis, and these T cells tended to be terminally differentiated effector cells. Based on this small cohort, these data suggest that even in the absence of disease, antigenic exposure may continually shape the CMV-responsive T cell population posttransplantation.


T cell biology; basic (laboratory) research/science; flow cytometry; immune regulation; immunobiology; infection and infectious agents; infectious disease; viral: Cytomegalovirus (CMV)

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