Is secreted IL-1 necessary for normal human T-cell activation?
The role of secreted and membrane-bound IL-1 in the activation of human T cells by monocyte-associated, processed antigen was examined. The IL-1 is secreted from antigen-pulsed plastic-adherent monocytes for only 24 h after isolation. After extensive washing, however, these monocytes are fully capable of stimulating T cells to proliferate. The T cells require less than 24 h of exposure to the monocytes to become activated and can then be cultured alone in fresh media. Addition of exogenous IL-1 does not enhance T-cell responsiveness in this model. Anti-IL-1 beta antibody does not inhibit the response, although we observed that pulsed monocytes have significant membrane-bound IL-1 assayed as biologic activity in the murine thymocyte costimulator assay. These studies suggest that secreted IL-1 is not required for the activation of human T cells and that membrane-bound IL-1 serves this function. The data further suggest that these two forms of IL-1 may be functionally distinct and that IL-1 beta is not the major component of membrane-bound IL-1. The possible relationship of these findings to the clinical efficacy of IL-1 inhibitors, such as corticosteroids, is discussed.
Goeken
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NE
Department of Medicine, Veterans Administration, Medical Center, Iowa City, IA 52240.
Staggs
T S
TS
D000937:Antigen-Antibody Reactions; D000954:Antigens, Surface / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D000954:Antigens, Surface; D007375:Interleukin-1