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.
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.
Ribbens
C
C
Division of Immunology and Allergy, Department of Internal Medicine, University Hospital, Geneva, Switzerland.
Dayer
J M
JM
Chizzolini
C
C
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018845:CD11 Antigens / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D002450:Cell Communication / Q000276:immunology; D018920:Coculture Techniques; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D019409:Interleukin-15 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018845:CD11 Antigens; D019013:CD40 Antigens; D023201:CD40 Ligand; D007375:Interleukin-1; D019409:Interleukin-15; D007376:Interleukin-2; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D000099192:CD69 Antigens