Association of Premature Immune Aging and Cytomegalovirus After Solid Organ Transplant

Immune function is altered with increasing age. Infection with cytomegalovirus (CMV) accelerates age-related immunological changes resulting in expanded oligoclonal memory CD8 T cell populations with impaired proliferation, signaling, and cytokine production. As a consequence, elderly CMV seropositi...

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Bibliographic Details
Main Authors: Lauren E. Higdon, Claire E. Gustafson, Xuhuai Ji, Malaya K. Sahoo, Benjamin A. Pinsky, Kenneth B. Margulies, Holden T. Maecker, Jorg Goronzy, Jonathan S. Maltzman
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.661551/full
Description
Summary:Immune function is altered with increasing age. Infection with cytomegalovirus (CMV) accelerates age-related immunological changes resulting in expanded oligoclonal memory CD8 T cell populations with impaired proliferation, signaling, and cytokine production. As a consequence, elderly CMV seropositive (CMV+) individuals have increased mortality and impaired responses to other infections in comparison to seronegative (CMV–) individuals of the same age. CMV is also a significant complication after organ transplantation, and recent studies have shown that CMV-associated expansion of memory T cells is accelerated after transplantation. Thus, we investigated whether immune aging is accelerated post-transplant, using a combination of telomere length, flow cytometry phenotyping, and single cell RNA sequencing. Telomere length decreased slightly in the first year after transplantation in a subset of both CMV+ and CMV– recipients with a strong concordance between CD57+ cells and short telomeres. Phenotypically aged cells increased post-transplant specifically in CMV+ recipients, and clonally expanded T cells were enriched for terminally differentiated cells post-transplant. Overall, these findings demonstrate a pattern of accelerated aging of the CD8 T cell compartment in CMV+ transplant recipients.
ISSN:1664-3224