CD40-CD40 ligand (CD154) engagement is required but may not be sufficient for human T helper 1 cell induction of interleukin-2- or interleukin-15-driven, contact-dependent, interleukin-1beta production by monocytes

Immunology. 2000 Feb;99(2):279-86. doi: 10.1046/j.1365-2567.2000.00948.x.


To investigate whether antigen-independent, interleukin-2 (IL-2) or IL-15 activation of polarized T helper (Th) cells would result in contact-dependent activation of monocytes, living Th1 and Th2 cell clones were co-cultured with THP-1 cells or fresh peripheral blood monocytes. Under these conditions IL-1beta production was induced almost exclusively by Th1 cells and was dependent on the presence and dose of IL-2 or IL-15, and on cell-cell contact, as demonstrated by double-chamber cultures. Low levels of IL-1 receptor antagonist (IL-1Ra) were induced by Th1 and higher levels by Th2 cells. IL-10 production was similar in Th1/monocyte and Th2/monocyte co-cultures, thus arguing against preferential down-regulation of IL-1beta production by anti-inflammatory IL-10 in Th2 co-cultures. In addition, IL-4 and IL-10 neutralization did not result in enhanced IL-1beta production in Th2/monocyte co-cultures. Preferential expression on Th1 cells of CD11b correlated with their capacity to induce IL-1beta production by THP-1 cells in the presence of IL-2 or IL-15, but anti-CD11b monoclonal antibody could not inhibit this activity. Blockade of the CD40-CD40 ligand interaction resulted in inhibition of IL-1beta-inducing capacity while IL-1Ra induction was unaffected, a result previously unknown. This differential effect indicates the selective relevance of CD40-CD40 ligand engagement in inflammatory monocyte responses upon activation by T cells. CD40 ligand expression levels did not differ in Th1 and Th2 cell clones, thus indicating that additional, unidentified molecule(s) preferentially expressed by Th1 cells are involved in their IL-1beta induction capacity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD11 Antigens / metabolism
  • CD40 Antigens / immunology*
  • CD40 Ligand
  • Cell Communication / immunology
  • Coculture Techniques
  • Humans
  • Interleukin-1 / biosynthesis*
  • Interleukin-15 / immunology
  • Interleukin-2 / immunology
  • Lectins, C-Type
  • Ligands
  • Membrane Glycoproteins / immunology
  • Monocytes / immunology*
  • Th1 Cells / immunology*
  • Th2 Cells / immunology


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD11 Antigens
  • CD40 Antigens
  • CD69 antigen
  • Interleukin-1
  • Interleukin-15
  • Interleukin-2
  • Lectins, C-Type
  • Ligands
  • Membrane Glycoproteins
  • CD40 Ligand