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 the resting memory phenotype are present in the periphery of healthy cynomolgus 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 CD8 SP T cells was stable in cultures with either mitogen or anti-CD3 antibody stimulation. In spite of lacking CD28 expression, DP T cells showed similar proliferative ability and apoptosis sensitivity to CD4 SP and CD8 SP T cells. 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, cytotoxic activity was comparable to that of CD8 SP T cells. Fresh DP T cells killed target cells mainly by the perforin-granzyme pathway. In addition, fresh DP T cells expressed a high level of mRNA for IFN-gamma and produced a high level of IFN-gamma when they were activated by anti-CD3 antibody ligation. 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 corresponding clones with DP and CD4 SP phenotypes might be derived from the same ancestor T cell. These 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 cells, and that they might play protective and regulatory roles in secondary immune response in cynomolgus monkeys.
Nam
K
K
Tsukuba Primate Center, National Institute of Infectious Diseases, 1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan.
Akari
H
H
Terao
K
K
Shibata
H
H
Kawamura
S
S
Yoshikawa
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D008253:Macaca mulatta / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000502:physiology; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019014:fas Receptor / Q000502:physiology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor