title: Genetic determinism in the relationship between human CD4+ and CD8+ T lymphocyte populations?
abstract: The adaptive immune system in mammals acts in a coordinated manner to eliminate environmentally derived pathogens. Humans, mice and rats show within species variation in the levels and ratios of their peripheral CD4+ and CD8+ T cells and to a significant degree this variation is under the control of polymorphic genes. Whether genes act separately to specify CD4+ and CD8+ subpopulation levels or whether CD8+ variation is controlled through gene and environmental action on CD4+ cells or vice versa, is not known. We use a quantitative modelling approach in identical and non-identical female human twins to delineate the lines of control which act upon and between CD4+ and CD8+ subsets. The major findings of the study are: (1) genetic variation controls CD8+ T cell levels through two major routes-the first is via an effect on CD4+ T cells which accounts for the observed co-variation between CD4+ and CD8+ T cells, the second is through direct action on CD8+ T cell levels. (2) No evidence of a gene effect from CD8+ T cells on CD4+ cells is observed. Our findings have implications for the evolution of the complex defence system of which CD4+ and CD8+ T cells are a crucial part and encourage further work towards locating common pleiotropic quantitative trait loci responsible for variation in numbers of T cells.
authors.affiliation: Twin Research & Genetic Epidemiology Unit, St. Thomas' Hospital, London SE1 9RT, UK.
authors.forename: K R
authors.initials: KR
authors.lastname: Ahmadi
authors.forename: M A
authors.initials: MA
authors.lastname: Hall
authors.forename: P
authors.initials: P
authors.lastname: Norman
authors.forename: R W
authors.initials: RW
authors.lastname: Vaughan
authors.forename: H
authors.initials: H
authors.lastname: Snieder
authors.forename: T D
authors.initials: TD
authors.lastname: Spector
authors.forename: J S
authors.initials: JS
authors.lastname: Lanchbury
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018655:Lymphocyte Count; D008957:Models, Genetic; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic / Q000235:genetics; D014427:Twins / Q000235:genetics*; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics; D044465:White People / Q000235:genetics