Responsiveness of peripheral blood mononuclear cells from normal and atopic donors to microbial superantigens.
Patients with atopic dermatitis (AD) are frequently colonized with Staphylococcus aureus strains secreting exotoxins such as the staphylococcal enterotoxin B (SEB) and A (SEA). Nonetheless the role of SEB and SEA in AD is yet unknown. We analyzed the responsiveness of peripheral blood mononuclear cells (PBMCs) and isolated T cells from donors with AD and from normal donors to SEB and SEA. PBMCs as well as T cells from normal donors showed a significantly enhanced proliferation after stimulation with enterotoxin B, whereas the 3H-thymidine uptake of the T lymphocytes from patients with AD was markedly suppressed. Furthermore, we show that IFN-gamma mRNA and protein and mRNA for both chains of IL-12 (p35 and p40) are produced in human PBMCs from normal donors upon stimulation with SEB and SEA. In contrast to normal donors T cells from donors with AD predominantly express mRNA for IL-4, IL-5, and only diminished levels for IFN-gamma and IL-12 upon stimulation with SEB and SEA. Furthermore, in contrast to normal donors, PBMCs from donors with AD spontaneously produce high levels of IgE and express increased levels of CD23, the low-affinity receptor for IgE. Nonetheless, the superantigens by themselves, from 0.1 fg up to 1 microgram/10(6) cells, induced neither IgE secretion nor CD23 expression on PBMCs. Moreover, the addition of superantigens to IL-4-treated PBMC cultures diminished or totally suppressed the IL-4-induced IgE synthesis and CD23 expression. No differences were observed between PBMCs from normal donors of donors with AD. Both PBMCs isolated from normal and atopic donors produced high levels of soluble IL-4-receptor (up to 210 +/- 90 pg/ml). Addition of soluble IL-4-receptor to PBMC cultures downregulated the IL-4-induced IgE synthesis and CD23 expression in unstimulated as well as in SEB-stimulated PBMCs from normal donors and donors with AD. Our results suggest that superantigen-producing staphylococcal strains on the skin of patients with AD may modulate and/or amplify allergic inflammation.
König
B
B
Medizinische Mikrobiologie und Immunologie, Ruhr-Universität Bochum, Deutschland.
Neuber
K
K
König
W
W
D001483:Base Sequence; D003876:Dermatitis, Atopic / Q000097:blood*; D004768:Enterotoxins / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D017455:Receptors, IgE / Q000032:analysis; D018123:Receptors, Interleukin / Q000032:analysis; D019948:Receptors, Interleukin-4; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism
D004768:Enterotoxins; D012333:RNA, Messenger; D017455:Receptors, IgE; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D018089:Superantigens; D018664:Interleukin-12; D015847:Interleukin-4; C026066:enterotoxin A, Staphylococcal; D007073:Immunoglobulin E; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma