Malaria infection induces rapid elevation of the soluble fas ligand level in serum and subsequent T lymphocytopenia: Possible factors responsible forthe differences in susceptibility of two species of Macaca monkeys to Plasmodium coatneyi infection

The intraerythrocytic stage of the simian malaria parasite Plasmodium coatn eyi (CDC strain) was intravenously inoculated into two species of macaques with different susceptibilities to infection with this parasite, including four Japanese macaques (Macaca fuscata) and three cynomolgus macaques (M. f ascicularis). The Japanese macaques infected with P, coatneyi developed sev ere clinical manifestations similar to those of severe human malaria and ev entually became moribund, while the infected cynomolgus macaques, natural h osts of the parasite, exhibited no severe manifestation of disease except a nemia and finally recovered from the infection. In the infected Japanese ma caques, peripheral CD4(+) and CD8(+) T-cell populations were markedly decre ased and fragmentation of chromosomal DNA in peripheral blood mononuclear c ells was detected during the terminal period of infection, suggesting that apoptotic cell death was responsible at least in part for the T lymphocytop enia. Furthermore, soluble Fas ligand levels in sera of the infected Japane se macaques increased gradually to a markedly high level of 28.83 +/- 10.56 pg/ml (n = 4) when the animals became moribund. On the other hand, none of the infected cynomolgus monkeys exhibited either T lymphocytopenia or elev ated soluble Fas ligand level. These findings suggest that differences in i mmune response between the two species of macaque tested accounted for the contrasting outcomes after infection with the same isolate of malarial para site, and in particular that a profound T lymphocytopenia due to Fas-derive d apoptosis played a role in the fatal course of malaria in the infected Ja panese macaques.