Cell surface glycoproteins expressed on activated human T cells induce production of interleukin-1 beta by monocytic cells: a possible role of CD69
Isler, P.; Vey, E.; Zhang, J.H.; Dayer, J.M.
European Cytokine Network 4(1): 15-23
1993
ISSN/ISBN: 1148-5493 PMID: 8490101 Document Number: 416768
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 times 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. However, in freshly isolated T cells, anti-CD69 mAb inhibited -70% of monocytic IL-1-beta production, suggesting that CD69 is partially involved in monocyte activation by cell-cell contact. In addition to CD69, novel molecules, as yet not identified, may also be involved in this process, since no correlation between CD69 expression and IL-1-beta-inducing capacity was observed in HUT-78 cells.