Cell surface glycoproteins expressed on activated human T cells induce production of interleukin-1 beta by monocytic cells: a possible role of CD69.
In many immunoinflammatory diseases, macrophages, by producing interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha), stimulate protease secretion in fibroblasts, thus contributing to tissue destruction. Monocyte/macrophage activation is prompted by soluble factors released by activated T cells as well as by cell-cell contact. Indeed, previous studies have shown that monocytes exposed to paraformaldehyde (PFA)-fixed, activated T cells produced high amounts of IL-1 beta. In this report, we used the T cell line HUT-78 to further characterize the T cell factor(s) responsible for monocyte activation by cell-cell contact. After subcellular fractionation, most of the activity was found in the cellular membrane fraction of PHA/PMA-stimulated HUT-78 cells, and proved to be due to glycoproteins, following trypsin digestion and tunicamycin treatment. HUT-78 cells acquired the capacity to stimulate monocytic cells after as little as 1h of stimulation. De novo protein synthesis was required for the expression of the IL-1 beta inducing factor, as shown by cycloheximide treatment. When membrane proteins of PHA/PMA-stimulated HUT-78 cells were separated on SDS-polyacrylamide gel, a peak of stimulatory activity was observed at Mr--25-35 x 10(3). By using specific cytokine inhibitors or blocking mAbs, we ascertained that cell-associated cytokines (IL-1, IL-2, IFN gamma and GM-CSF) were not involved in monocyte activation by cell contact. Anti-CD2 and -CD11a (LFA-1) mAbs partially blocked IL-1 beta production by -25% and -35%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Isler
P
P
Division of Immunology and Allergy (Hans Wilsdorf Laboratory), Hôpital Cantonal Universitaire, Geneva, Switzerland.
Vey
E
E
Zhang
J H
JH
Dayer
J M
JM
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D008970:Molecular Weight; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010835:Phytohemagglutinins; D013347:Subcellular Fractions / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D013755:Tetradecanoylphorbol Acetate