Ligand binding to the LFA-3 cell adhesion molecule induces IL-1 production by human thymic epithelial cells

• Published in: The Journal of immunology (1950) Vol. 144; no. 12; pp. 4541 - 4547
• Main Authors: Le, PT, Vollger, LW, Haynes, BF, Singer, KH
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.06.1990; American Association of Immunologists
• Subjects: Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte - physiology; Antigens, Surface - physiology; Biological and medical sciences; Blotting, Northern; CD2 Antigens; CD58 Antigens; Cell Adhesion Molecules - physiology; Cells, Cultured; Cycloheximide - pharmacology; Dactinomycin - pharmacology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Humans; Immunobiology; In Vitro Techniques; Interleukin-1 - biosynthesis; Interleukin-1 - genetics; Ligands; Lymphoid organs: ontogeny, organization, homing phenomenon; Membrane Glycoproteins - physiology; Receptors, Immunologic - physiology; RNA, Messenger - genetics; Thymus Gland - physiology; Human; Ligand binding; Thymus gland; Interleukin 1; Cell adhesion molecule; Cytokine; Interleukin 1α; Epithelial cell; Cell cell interaction; Interleukin 1β; Biosynthesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.144.12.4541

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.