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Background: Cytomegalovirus (CMV) infection is one of the most common infections in humans, and CMV antigens are the major drivers of repetitive T-cell stimulation as a part of a well-adapted immune response in immunocompetent individuals. With higher age, the recurrent clonal expansion of CMV-specific T cells results in high frequencies of CMV-specific effector T cells. Further on, CMV seropositivity has been linked to an increased risk of developing cardiovascular diseases (CVD). Here we investigated the frequency and phenotype of CMV-specific T cells in the circulation of a population cohort of 650 individuals focusing on the age group over 60 years. Circulating immune cells of individuals carrying the HLA-A*02 allele were investigated (n = 302) applying MHC class I tetramers.
Results: We add to previous knowledge by showing that the frequency of CMVpp65-specific CD8 T cells is associated with the total percentage and absolute counts of CD8 and CD4CD8 double-positive T cells within leukocytes, and further with systolic blood pressure (SBP) and history of CVD. An investigation into the differentiation status of CMV-specific T cells revealed an association of higher age and increased frequencies of both T and CD27-expressing T cells. In contrast, higher CMV-IgG titers were found to be associated with T and CD27 T cell frequencies. SBP significantly correlated with CMV-specific effector CD8 T cells, which was mostly reflected by CD27 T cells.
Conclusions: Within the circulating CMV-specific T cell population, different effector T-cell subtypes were associated with age, serostatus and SBP. This suggests that it is not age or infection per se that render CMV-positive individuals susceptible to CVD, but rather the cellular immune response to CMV. Detailed immunophenotyping may identify individuals whose immune systems are strongly influenced by the response to CMV, leading to health consequences and impairing healthy aging.
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http://dx.doi.org/10.1186/s12979-025-00523-x | DOI Listing |
Lancet Microbe
August 2025
Microbiology and Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy.
Background: Vertical transmission of human cytomegalovirus (CMV) to the fetus (congenital CMV infection) can occur in pregnant women with preconception immunity. Maternal immunological features associated with congenital CMV infection have been poorly investigated. We aimed to characterise the immunological features of pregnant women with preconception immunity in cases with and without vertical transmission of human CMV to the fetus.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2025
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
This study examines the expression of CD45 isoforms on human yellow fever virus vaccine (YFV-17D) specific CD8 T cells longitudinally after vaccination. As expected, effector CD8 T cells at day 14 express CD45RO but within 4 to 6 wk these virus-specific CD8 T cells become CD45RA positive and remain CD45RA for >10 y. The journey for these YFV-specific CD8 T cells goes from naive (CD45RA+ CCR7+) to effector/effector memory (CD45RO+ CCR7-) to Temra (CD45RA+ CCR7-) to stem-cell memory (CD45RA+ CCR7+).
View Article and Find Full Text PDFTranspl Int
July 2025
Department of Nephrology, Transplantation, Dialysis and Apheresis, Bordeaux University Hospital, Bordeaux, France.
Evaluation of CMV-specific cell-mediated immunity (CMI) has improved strategies to prevent post-transplant CMV disease. This study assessed the association between CMV disease and absolute count of TEMRA γδ T cells at the end of universal prophylaxis in kidney transplant recipients (KTR). We retrospectively analyzed 262 R⁺ and 82 D⁺/R⁻ KTRs who received antiviral prophylaxis and had TEMRA γδ T cells quantified at the end of prophylaxis.
View Article and Find Full Text PDFUnlabelled: Patients who are recipients of allogeneic transplants or have underlying autoimmune disease require immune suppression, often with calcineurin inhibitors (CNI). There is an expanding repertoire of immune effector cell (IEC) therapies, including CD19 CAR-T cells and viral-specific T cells (VSTs), deployed in these patients; however, ongoing CNI therapy may be detrimental to IEC function. We thus developed a CRISPR/Cas9-based approach to engineer dual CNI [cyclosporine (CsA) and voclosporin (VCS)] resistant IEC therapies by targeting (encoding cyclophilin A - CypA), a critical binding partner for both drugs.
View Article and Find Full Text PDFImmun Ageing
July 2025
Department of Dermatology and Allergy, Hannover Medical School (MHH), Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Background: Cytomegalovirus (CMV) infection is one of the most common infections in humans, and CMV antigens are the major drivers of repetitive T-cell stimulation as a part of a well-adapted immune response in immunocompetent individuals. With higher age, the recurrent clonal expansion of CMV-specific T cells results in high frequencies of CMV-specific effector T cells. Further on, CMV seropositivity has been linked to an increased risk of developing cardiovascular diseases (CVD).
View Article and Find Full Text PDF