title: Are CD4+ Th1 cells pro-inflammatory or anti-inflammatory? The ratio of IL-10 to IFN-gamma or IL-2 determines their function.
abstract: Human CD4+ T cells have, like their murine counterparts, been classified on the basis of their cytokine profile. Th1 cells produce IL-2 and IFN-gamma, but little or no IL-4. Th2 cells produce IL-4 but not IFN-gamma or IL-2, and Th0 produce IL-2, IL-4 and IFN-gamma. As IL-2 is the most potent T cell growth factor and IFN-gamma is the strongest activator of macrophages it is not surprising that CD4+ Th1 cells are considered to be pro-inflammatory. However, unlike results in the mouse, where IL-10 is only produced by Th2 cells, human IL-10 is produced by Th0, Th1 and Th2 cells. Hence some human Th1 cells are capable of producing both pro-inflammatory (IL-2, IFN-gamma) and anti-inflammatory (IL-10) cytokines, therefore the function of these cells may not be accurately encapsulated by the 'Th1' terminology. We thus investigated the correlation of cytokine production and function in human CD4+ Th1 clones. Cytokine production (IL-2, IFN-gamma, IL-10) was measured in supernatants by ELISA after stimulation with solid-phase anti-CD3. The capacity of these supernatants to activate or inhibit T cell proliferation or LPS induced TNF-alpha production by monocytes was assessed. The ratio of IL-2/IL-10 or IFN-gamma/IL-10 was of critical importance in determining the function of the supernatants. The inhibitory effects were verified to be due to IL-10, as they were neutralized by anti-IL-10 mAb.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002460:Cell Line; D002474:Cell-Free System / Q000276:immunology; D002999:Clone Cells; D000939:Epitopes; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects; D018417:Th1 Cells / Q000145:classification* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D000939:Epitopes; D007376:Interleukin-2; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma