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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.

Author information

1
Department of Medicine/Nephrology, Stanford University, Palo Alto, CA.
2
Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, PA.
3
Perelman School of Medicine, University of Pennsylvania, Renal Division, Philadelphia, PA.
4
Perelman School of Medicine, University of Pennsylvania, Cardiovascular Institute, Philadelphia, PA.
5
Stanford University, School of Medicine, Department of Pathology, Stanford, CA.
6
Perelman School of Medicine, University of Pennsylvania, Infectious Diseases Division, Philadelphia, PA.
7
Stanford University, School of Medicine, Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford, CA.
8
VA Palo Alto Health Care System, Palo Alto, CA.

Abstract

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.

KEYWORDS:

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

PMID:
28199780
PMCID:
PMC5519416
DOI:
10.1111/ajt.14227
[Indexed for MEDLINE]
Free PMC Article

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