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CD95 (Fas)-based, superantigen-dependent, CD4+ T cell-mediated down-regulation of human in vitro immunoglobulin responses.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1998 Jun 01; Vol. 160 (11), pp. 5231-8. - Publication Year :
- 1998
-
Abstract
- Naturally occurring microbial superantigens (SAg) have been implicated in several human idiopathic disorders, and a compelling argument for the role of SAg in autoantibody-associated disorders, such as systemic lupus erythematosus, has been proposed. To test the effects of SAg on human in vitro Ig responses, CD4+ T cell + B cell cultures were stimulated with graded doses of staphylococcal enterotoxin B (SEB). Ig-secreting cell (IgSC) responses were very weak in CD4+ T cell + B cell cultures stimulated with SEB at the optimal mitogenic concentration (high dose SEB; 100 ng/ml) but were strong in parallel cultures stimulated with low dose SEB (0.01 ng/ml). High dose SEB actually enhanced B cell differentiation in the presence of CD4+ T cell soluble helper factors as long as the B cells were prevented from physically contacting the CD4+ T cells. However, when cell-cell contact between CD4+ T cells and B cells was permitted, high dose, but not low dose, SEB promoted increased CD4+ T cell-mediated B cell apoptosis with resulting decreases in viable CD20+ B cells and IgSC. High dose, but not low dose, SEB triggered increased levels of soluble CD95 ligand, and down-regulation of IgSC responses and incremental apoptosis of activated B cells were prevented by antagonist anti-CD95 mAb. This strongly suggests that CD4+ T cell-mediated CD95-based killing of activated B cells plays a major role in controlling SEB-driven IgSC responses. Defects in SAg-based down-regulation may contribute to autoimmune disorders such as SLE.
- Subjects :
- Antibodies, Monoclonal pharmacology
Apoptosis immunology
B-Lymphocytes cytology
B-Lymphocytes immunology
B-Lymphocytes metabolism
Cell Communication immunology
Cell Differentiation immunology
Cell-Free System
Cells, Cultured
Dose-Response Relationship, Immunologic
Enterotoxins pharmacology
Fas Ligand Protein
Hemolytic Plaque Technique
Humans
Interleukin-2 physiology
Ligands
Lymphocyte Activation
Lymphocyte Cooperation immunology
Lymphocyte Count
Membrane Glycoproteins metabolism
Recombinant Proteins pharmacology
Solubility
Staphylococcus aureus immunology
fas Receptor biosynthesis
fas Receptor immunology
CD4-Positive T-Lymphocytes immunology
Down-Regulation immunology
Immunoglobulins biosynthesis
Superantigens pharmacology
fas Receptor physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 160
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 9605118