Interleukin-10-mediated T cell apoptosis during the T helper type 2 cytokine 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 Th2 cytokine switch, associated with a pathogenic granulomatous response to parasite eggs and to a global defect in Th1-cell effector functions. Here we report that the Th2 cytokine response, which begins 6 weeks after infection, at the time of parasite egg laying (i) does not occur in the context of a genuine Th1 to Th2 cytokine switch, but is associated 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 significant fraction of the CD4 and CD8 T cells, which is greatly enhanced by TCR stimulation; and (iii) is associated, in vivo, with numerous and large clusters of apoptotic cells in the spleen and in the inflammatory infiltrates surrounding the parasite egg deposits in the liver. The 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 effect 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 activation-induced premature T cell death, that include Th1 (or Th0) cells. Further identification of mechanisms involved in the regulation of T cell apoptosis has implications for the understanding of the pathogenesis of immunosuppression associated with chronic infectious diseases.
Estaquier
J
J
INSERM U. 415, Institut Pasteur de Lille, France.
Marguerite
M
M
Sahuc
F
F
Bessis
N
N
Auriault
C
C
Ameisen
J C
JC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D018076:DNA, Complementary; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10