Peripheral blood extrathymic CD4(+)CD8(+) T cells with high cytotoxic activity are from the same lineage as CD4(+)CD8(-) T cells in cynomolgus monkeys

We have previously reported that CD4/CD8 double-positive (DP)T cells with t he resting memory phenotype are present in the periphery of healthy cynomol gus monkeys, In the present study, we performed functional studies on the T cells. The expression of CD4 and CD8 on DP, CD4 single-positive (SP) or CD 8 SP T cells was stable in cultures with either mitogen or anti-CD3 antibod y stimulation. In spite of lacking CD28 expression, DP T cells showed simil ar proliferative ability and apoptosis sensitivity to CD4 SP and CD8 SP T c ells. DP T cells showed both helper and cytotoxic activities. Although the helper activity of DP T cells was lower than that of CD4 SP T cells, cytoto xic activity was comparable to that of CD8 SP T cells. Fresh DP T cells kil led target cells mainly by the perforin-granzyme pathway. In addition, fres h DP T cells expressed a high level of mRNA for IFN-gamma and produced a hi gh level of IFN-gamma when they were! activated by anti-CD3 antibody ligati on, On the other hand, several expanded DP T cell clones shared TCR V-beta with expanded CD4 SP T cell clones, strongly suggesting that those two corr esponding clones with DP and CD4 SP phenotypes might be derived from the sa me ancestor T cell. Thesis results showed that the DP T cells are a novel T cell subset with functions overlapping with those of CD4 SP and CD8 SP T c ells, and that they might play protective and regulatory roles in secondary immune response in cynomolgus monkeys.