T regulatory-1 cells induce IgG4 production by B cells: role of IL-10.
The study was aimed to find out whether T cells with a regulatory profile could regulate the secretion of IgG4. Using tetanus Ag we found that PBMC of healthy human donors responded to exogenous IL-10 by down-regulating IgG1 and increasing IgG4 secretion. IgE was not affected. To investigate the direct effect of IL-10-producing T cells on B cells, we generated T cell clones (TCC) with two different cytokine profiles: first, IL-10high, IL-2low, IL-4low TCC, and second, IL-10low, IL-2high, IL-4high. The T cell-dependent Ab secretion was measured by coculturing purified CD19+ B cells and the TCC. Interestingly, we found that IgG4 production in the coculture correlated with the TCC production of IL-10 (r2 = 0.352, p = 0.0001), but not with IL-2, IL-4, nor IFN-gamma. IgE showed only a trend with regard to IL-4. Further, there was decreased Ab secretion in the absence of T-B cell contact. IL-10 also induced IgG4 when added to a Th1 TCC-B cell coculture system. The present study thus shows that in T-B cell coculture, IL-10, if induced by the TCC or added to the system, down-regulates the immune response by inducing IgG4 secretion. This establishes a direct implication of IL-10 in humoral hyporesponsiveness, particularly in compartments where the T-B cell interplay determines the subsequent immune response. The correlation between IgG4 and IL-10 (r2 = 0.352) indicates that IL-10 is an important but not the only factor for IgG4 induction.
Satoguina
Judith S
JS
Institute of Medical Parasitology, Friedrich Wilhelm University of Bonn, Bonn, Germany.
Weyand
Esther
E
Larbi
John
J
Hoerauf
Achim
A
D000941:Antigens; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000494:pharmacology; D008211:Lymphocyte Cooperation; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D000941:Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D013745:Tetanus Toxoid; D016753:Interleukin-10