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

J Immunol. 1990 Jun 15;144(12):4541-7.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte / physiology
  • Antigens, Surface / physiology*
  • Blotting, Northern
  • CD2 Antigens
  • CD58 Antigens
  • Cell Adhesion Molecules / physiology*
  • Cells, Cultured
  • Cycloheximide / pharmacology
  • Dactinomycin / pharmacology
  • Gene Expression
  • Humans
  • In Vitro Techniques
  • Interleukin-1 / biosynthesis*
  • Interleukin-1 / genetics
  • Ligands
  • Membrane Glycoproteins / physiology*
  • RNA, Messenger / genetics
  • Receptors, Immunologic / physiology
  • Thymus Gland / physiology*


  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Surface
  • CD2 Antigens
  • CD58 Antigens
  • Cell Adhesion Molecules
  • Interleukin-1
  • Ligands
  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Immunologic
  • Dactinomycin
  • Cycloheximide