title: Genetic Influence on the Peripheral Blood CD4+ T-cell Differentiation Status in CMV Infection.
abstract: A latent infection with cytomegalovirus (CMV), a ubiquitous beta herpesvirus, is associated with an accumulation of late-differentiated memory T-cells, often accompanied by a reciprocal reduced frequency of early-differentiated cells (commonly also referred to as "naïve"). However, this impact of CMV on T-cell phenotypes is variable between individuals. Our previous findings in a subgroup of participants in the Leiden familial Longevity Study indicated an important role of genetics. For further testing, we have analyzed middle-aged monozygotic (MZ, n = 42) and dizygotic (DZ, n = 39) twin pairs from the Danish Twin Registry for their T-cell differentiation status, assessed by surface expression of CD27, CD28, CD57, and KLRG-1. We observed a significant intraclass correlation between cotwins of MZ, but not DZ pairs for the differentiation status of CD4+and CD8+subsets. Classical heritability analysis confirmed a substantial contribution of genetics to the differentiation status of T-cells in CMV infection. The humoral (IgG) response to different CMV antigens also seems to be genetically influenced, suggesting that a similar degree of immune control of the virus in MZ twins might be responsible for their similar T-cell differentiation status. Thus, the way T-cells differentiate in the face of a latent CMV infection, and the parallel humoral responses, both controlling the virus, are genetically influenced.
authors.affiliation: Second Department of Internal Medicine, Center for Medical Research, University of Tübingen Medical School, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Goldeck
authors.affiliation: The Danish Twin Registry, University of Southern Denmark, Odense.
authors.forename: Lisbeth Aagaard
authors.initials: LA
authors.lastname: Larsen
authors.affiliation: The Danish Twin Registry, University of Southern Denmark, Odense.
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
authors.affiliation: The Danish Twin Registry, University of Southern Denmark, Odense.|Department of Clinical Genetics and.|Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark.
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.affiliation: Institute of Medical Virology, University of Tübingen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Hamprecht
authors.affiliation: Second Department of Internal Medicine, Center for Medical Research, University of Tübingen Medical School, Germany. graham.pawelec@uni-tuebingen.de.
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
authors.affiliation: Second Department of Internal Medicine, Center for Medical Research, University of Tübingen Medical School, Germany.|Present address: BioNTech AG, An der Goldgrube 12, D-55131 Mainz, Germany.
authors.forename: Evelyna
authors.initials: E
authors.lastname: Derhovanessian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000276:immunology*; D003718:Denmark; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D056724:Immunity, Humoral; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D008136:Longevity; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype
chemical_list: D007074:Immunoglobulin G
keywords: Genetics; Heritability; Humoral responses; Twins