title: Human Th1 cells preferentially induce interleukin (IL)-1beta while Th2 cells induce IL-1 receptor antagonist production upon cell/cell contact with monocytes.
abstract: The role of human T cells in the induction and regulation, upon cell/cell contact, of inflammatory responses by monocytic cells was investigated. The production of interleukin (IL)-1beta and IL-1 receptor antagonist (IL-1Ra) by the monocytic THP-1 cell line was measured upon contact with either Th1 or Th2 cell clones. CD4+ T cell clones specific for purified protein derivative of Mycobacterium tuberculosis, predominantly Th1 [high interferon (IFN)-gamma and low IL-4 producers], or tetanus toxoid, predominantly Th2 (low IFN-gamma and high IL-4 producers), were generated. Cell membranes from antigen-stimulated, but not from resting T cell clones induced dose-dependent cytokine production by THP-1 cells. Th1 clones induced higher levels of IL-1beta production (484-806 pg/ml) than did Th2 clones (21-114 pg/ml). In contrast, Th1 clones induced lower levels of IL-IRa (0.9-7.8 ng/ml) than did Th2 clones (7.0-49.6 ng/ml). Similar results were obtained when T cell clones were activated by cross-linked CD3 and CD28. IL-1beta production by THP-1 cells correlated with IFN-gamma production by T cell clones but was unaffected by IFN-gamma neutralization. IL-1Ra production by THP-1 cells correlated with IL-4 production by T cells and was partially inhibited by IL-4 neutralization. These data indicate that activated Th1 and Th2 cells express different molecules on the cell surface able to induce distinct pro-inflammatory (IL-1beta) or anti-inflammatory (IL-1Ra) responses in monocytes. This differential induction of molecules with opposite effects on inflammation stresses the functional heterogeneity in CD4+ T cells.
authors.affiliation: Department of Internal Medicine, Hôpital Cantonal Universitaire, Geneva, Switzerland. chizzoli@epicure.hcuge.ch
authors.forename: C
authors.initials: C
authors.lastname: Chizzolini
authors.forename: R
authors.initials: R
authors.lastname: Chicheportiche
authors.forename: D
authors.initials: D
authors.lastname: Burger
authors.forename: J M
authors.initials: JM
authors.lastname: Dayer
mesh_terms: D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D002448:Cell Adhesion; D002450:Cell Communication; D002455:Cell Division; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007371:Interferon-gamma / Q000096:biosynthesis; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D015847:Interleukin-4; D007371:Interferon-gamma