Genetic determinism in the relationship between human CD4+ and CD8+ T lymphocyte populations?

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.