Ligand binding to the LFA-3 cell adhesion molecule induces IL-1 production by human thymic epithelial cells
Autor: | P T, Le, L W, Vollger, B F, Haynes, K H, Singer |
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Rok vydání: | 1990 |
Předmět: |
Antigens
Differentiation T-Lymphocyte Membrane Glycoproteins CD2 Antigens Antibodies Monoclonal Gene Expression Thymus Gland In Vitro Techniques Blotting Northern CD58 Antigens Ligands Antigens Surface Dactinomycin Humans RNA Messenger Cycloheximide Receptors Immunologic Cell Adhesion Molecules Cells Cultured Interleukin-1 |
Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 144(12) |
ISSN: | 0022-1767 |
Popis: | We have shown that human thymic epithelial (TE) cells produce IL-1 alpha, IL-1 beta, and TE cells bind to thymocytes by CD2 and LFA-1 molecules on thymocytes and LFA-3, ICAM-1 on TE cells. We investigated whether ligand binding to LFA-3 on human TE cells can modulate TE cell IL-1 production. First, we investigated the ability of human thymocytes to regulate IL-1 release by TE cells. Both autologous and allogenic emetine-treated thymocytes when cultured with TE cells augmented IL-1 release by TE cells. The augmentation of IL-1 release was cell density dependent. Inasmuch as the interaction between thymocytes and TE cells is mediated in part by CD2 molecules on thymocytes and LFA-3 molecules on TE cells we next determined the effect on IL-1 release of ligand binding (anti-LFA-3 mAb TS2/9) to TE cell surface LFA-3. Purified anti-LFA-3 mAb augmented IL-1 release in a concentration-dependent fashion. The anti-LFA-3-mediated augmentation of IL-1 release required both new protein and RNA synthesis as shown by the ability of cycloheximide and actinomycin-D to inhibit augmentation of IL-1 production by TE cells, and by direct quantitation of IL-1 alpha and IL-1 beta mRNA by Northern blot analysis. Both F(ab)'2 and Fab' fragments of anti-LFA-3 mAb augmented IL-1 alpha and IL-1 beta mRNA production, indicating that monovalent binding to cell surface LFA-3 was sufficient to provide the inducing signal. The identification of LFA-3, the cell surface ligand for thymocyte CD2 molecules, as a molecule via which TE cell-derived cytokine production may be regulated suggests a mechanism at the cell surface by which direct TE cell-thymocyte interaction might result in the triggering of local IL-1 release within the human thymic microenvironment. |
Databáze: | OpenAIRE |
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