The role of IL-4 in the staphylococcal enterotoxin B-triggered immune response: increased susceptibility to shock and deletion of CD8Vbeta8+ T cells in IL-4 knockout mice.
Administration of superantigens in vivo triggers responding T cells into clonal expansion and subsequent activation of the programmed cell death pathway, as well as into anergy. We examined the possibility that Th1 cytokines are involved in rescue from superantigen-induced programmed cell death and prevention of anergy by studying the Staphylococcus aureus enterotoxin B (SEB) immune response in mice in which the IL-4 gene was deleted (IL-4-/-). In these mice, Th1 cell activation triggers increased IFN-gamma and reduced IL-5 production as compared to IL-4+/+ mice. The primary anti-SEB antibody response in IL-4-/- mice is thus dominated by immunoglobulins of the IgG2a isotype, whereas the IgG1 isotype prevails in IL-4+/+ mice. Our results also show that, in contrast to expectations, IL4-/- mice are more susceptible to SEB plus low-dose D-galactosamine-induced shock and that this response is TNF-alpha-dependent. In vivo treatment induces partial deletion and anergy of remaining SEB-reactive T cells. During the SEB-induced response, CD4Vbeta8+ T cells are deleted in IL-4-/- mice, but not in IL-4+/+ mice, suggesting a function for IL-4 in CD8+ T cell rescue from apoptosis. We show that IL-4 efficiently protects CD8+ T cells from in vitro starvation-induced apoptosis, and conclude that IL-4 has an important role in Th1 immune response regulation.
Aroeira
L S
LS
Department of Immunology and Oncology, Centro Nacional de Biotecnología, CSIC, Universidad Autónoma de Madrid, Spain. laroeira@net.ipen.br
Martínez-A
C
C
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D012772:Shock, Septic / Q000209:etiology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D004768:Enterotoxins; D007074:Immunoglobulin G; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; C031818:enterotoxin B, staphylococcal