INTERLEUKIN-10 - MEDIATED T-CELL APOPTOSIS DURING THE T-HELPER TYPE-2CYTOKINE RESPONSE IN MURINE SCHISTOSOMA-MANSONI PARASITE INFECTION

The pathogenesis of infection with the helminth parasite Schistosoma ( S) mansoni in mice has been reported to involve a T helper (Th)1 to Th 2 cytokine switch, associated with a pathogenic granulomatous response to parasite eggs and to a global defect in Th1-cell effector function s, Here we report that the Th2 cytokine response, which begins 6 weeks after infection, at the time of parasite egg laying (i) does not occu r in the context of a genuine Th1 to Th2 cytokine switch, but is assoc iated with a persistent capacity of Th1 (or Th0) cells to secrete IL-2 and IFN-gamma in response to T cell receptor (TCR) stimulation; (ii) is associated, in vitro, with spontaneous death by apoptosis of a sign ificant fraction of the CD4 and CD8 T cells, which is greatly enhanced by TCR stimulation; and (iii) is associated, in vivo, with numerous a nd large clusters of apoptotic cells in the spleen and in the inflamma tory infiltrates surrounding the parasite egg deposits in the liver, T he in vitro addition of antibodies to the Th2 cytokine IL-10 had both a preventive effect on TCR-induced T cell apoptosis and an enhancing e ffect on TCR-induced T cell secretion of Th1 cytokines, Taken together , these findings suggest that the downregulation of Th1-cell-mediated effector functions in S. mansoni-infected mice may not be related to a lack of Th1 cell production, but to a process of IL-10-mediated and a ctivation-induced premature T cell death, that include Th1 (or Th0) ce lls, Further identification of mechanisms involved in the regulation o f T cell apoptosis has implications for the understanding of the patho genesis of immunosuppression associated with chronic infectious diseas es.