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Possible role of genetic factor(s) on age-related increase of peripheral CD4+CD8+ double positive T cells in cynomolgus monkeys.

Mature TCR alpha beta T cells in peripheral blood are generally classified into either CD4 single positive (sp) T cells or CD8sp T cells. Several studies demonstrated that considerable amounts of CD4+CD8+ double positive (DP) T cells exist in peripheral blood of human and several animals. In particular, we previously reported that peripheral DP T cells increase in an age-related manner in cynomolgus monkeys (Macaca fascicularis), but the finding that DP T cells in some aged monkeys were maintained at a low proportion (under 5%), suggests that the increase in peripheral DP T cells might be genetically controlled in cynomolgus monkeys. To test this hypothesis, 24 families were randomly selected and used in a formal genetic analysis of the proportion of DP T cells. Parents and offspring in selected families were classified into DP-High and DP-Low groups based on a 5% cutoff level of DP T cells. The cutoff value was set by analysis of the distribution of the proportion of DP T cells. Nine out of 13 offspring (69.2%) with DP-High x DP-High parents belonged to the DP-High group, whereas three out of nine offspring (33.3%) belonged to DP-High group in the case of DP-High x DP-Low mating pairs. No offspring (0%) of two offspring with DP-Low x DP-Low parents belonged to the DP-High group. In addition, heritability (h2: narrow sense) obtained from the regression coefficient of offspring on mid-parent values was 0.54 +/- 0.19. Both findings suggest that increases in DP T cells in cynomolgus monkeys may be genetically controlled.