Age-related increase of peripheral CD4+ CD8+ double-positive T lymphocytes in cynomolgus monkeys: longitudinal study in relation to thymic involution.

Abstract

The age-related increase of peripheral CD4+ CD8+ double-positive (DP) T cells in cynomolgus monkeys has been reported previously. Because the percentage of DP T cells in cynomolgus monkeys increases abruptly in parallel with the thymic involution occurring at around 11 years of age, it was suggested that thymic involution was associated with this increase. Therefore, a longitudinal study was carried out over 5 years to clarify the exact time when DP T lymphocytes start to increase in relation to the thymic involution. Twelve cynomolgus monkeys at 6 years of age were classified into three groups, based on their percentage of DP T cells, as follows: DP-High (>5% DP T cells); DP-Middle (1-5% DP T cells); and DP-Low (<1% DP T cells). In the DP-High group, the percentage of DP T cells showed an abrupt increase, of >10%, in monkeys at 7 years of age, and the prevalence of this subset correlated with a distinctive increase in the percentage of memory T cells (CD4+ CD29(high), CD8+ CD28-), indicating an association with the maturation of immune function, including thymic involution. To assess the thymic function, the coding joint of T-cell receptor excision circles (cjTREC) levels in sorted T cells were analysed by polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay (ELISA). The cjTREC in the T cells of the DP-High group (4362 +/- 3139 copies/105 T cells) was significantly lower than that (22 722 +/- 4928 copies/105 T cells) of the DP-Low group. Moreover, the mean copy number of cjTREC in naive T cells was also significantly different between the DP-High and the DP-Low group (0.457 +/- 0.181 and 1.141 +/- 0.107, respectively). These findings suggest that thymic involution has an influence on the age-related increase of DP T cells in cynomolgus monkeys.