Genetic polymorphisms in mouse genes regulating age-sensitive and age-stable T cell subsets.

To see whether genetic polymorphisms regulate inter-individual differences in T cell subset levels, we have conducted a genome scan in two populations of mice, bred as the progeny of a cross between CB6F1 females and C3D2F1 males. The data document quantitative trait loci (QTL) with statistically significant effects on CD4, CD8, and CD8 memory T cells, and on subsets of CD4 and CD8 T cells that express P-glycoprotein. Some of the loci detected were robust, in the sense that they produced effects of similar size both in mated female mice, and in a population that included male and female virgin animals. Some of the effects were stable, in that they were apparent at both 8 and 18 months of age, but others were age-specific, showing effects either at 8 or at 18 months but not at both ages. Genes that had an effect on the same T cell subset were in almost all cases additive rather than epistatic, and their combined effects could produce large overall effects, leading in the most dramatic case to a two-fold difference in CD8 memory cells. The analysis also documented two QTL, on chromosomes 4 and 13, that regulate an age-sensitive composite index of T cell subset pattern which has been shown previously to be a predictor of life expectancy in these mice. The analysis thus reveals both subset-specific genes and others which modulate the overall pattern of age-sensitive changes in T cell subset distributions.