Suppression of Ag-induced release of EP (IL 1) by spleen cells of specifically desensitized donors: evidence for the role of a suppressor cell.
Monocytes or macrophages may be induced to produce IL 1 by activators (e.g., lipopolysaccharide endotoxin) that act directly or by antigens/mitogens (e.g., Con A) that stimulate inducer lymphocytes to release a lymphokine that stimulates macrophages. Using guinea pigs (GP) rendered delayed hypersensitive to ovalbumin (OVA), we investigated the role of spleen cells from normal, sensitized, and specifically desensitized GP in suppressing release of IL 1, measured as endogenous pyrogen (EP), from peritoneal exudates of sensitized GP when incubated with OVA in vitro. Co-cultivation of all three sources of spleen cells with GP peritoneal exudate cells and OVA suppressed EP release as measured in the rabbit fever assay, the effect being most marked with cells from desensitized GP, intermediate with cells from sensitized GP, and least with normal cells. This suppressor activity of spleen cells on in vitro EP release was not explained by nonspecific absorption of EP by the added cells and did not affect EP release by a stimulus that activates macrophages directly (heat-killed staphylococci). It required both lymphocytes and macrophages for its effect, but unlike some other suppressor factors, it was not modified by indomethacin, an inhibitor of prostaglandin release. This appears to be the first reported evidence for cell-mediated suppression of lymphokine-mediated release of IL 1, an important modulator of the immune system through its combined role as a lymphocyte-activating factor and an inducer of fever (EP).
Atkins
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Francis
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D000818:Animals; D000941:Antigens / Q000276:immunology*; D001202:Ascitic Fluid / Q000276:immunology; D002448:Cell Adhesion; D003524:Cyclosporins / Q000494:pharmacology; D003888:Desensitization, Immunologic; D005260:Female; D006168:Guinea Pigs; D007375:Interleukin-1 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D014176:Protein Biosynthesis; D011817:Rabbits; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013210:Staphylococcus / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
D000941:Antigens; D003524:Cyclosporins; D007375:Interleukin-1; C008270:leukocyte endogenous mediator; D010047:Ovalbumin