Interferon-lambda enhances adaptive mucosal immunity by boosting release of thymic stromal lymphopoietin
NATURE IMMUNOLOGY
Authors: Ye, Liang; Schnepf, Daniel; Becker, Jan; Ebert, Karolina; Tanriver, Yakup; Bernasconi, Valentina; Gad, Hans Henrik; Hartmann, Rune; Lycke, Nils; Staeheli, Peter
Abstract
Interferon-lambda (IFN-lambda) acts on mucosal epithelial cells and thereby confers direct antiviral protection. In contrast, the role of IFN-lambda in adaptive immunity is far less clear. Here, we report that mice deficient in IFN-lambda signaling exhibited impaired CD8(+) T cell and antibody responses after infection with a live-attenuated influenza virus. Virus-induced release of IFN-lambda triggered the synthesis of thymic stromal lymphopoietin (TSLP) by M cells in the upper airways that, in turn, stimulated migratory dendritic cells and boosted antigen-dependent germinal center reactions in draining lymph nodes. The IFN-lambda-TSLP axis also boosted production of the immunoglobulins IgG1 and IgA after intranasal immunization with influenza virus subunit vaccines and improved survival of mice after challenge with virulent influenza viruses. IFN-lambda did not influence the efficacy of vaccines applied by subcutaneous or intraperitoneal routes, indicating that IFN-lambda plays a vital role in potentiating adaptive immune responses that initiate at mucosal surfaces.
CYTOKINES, IMMUNOGLOBULINS AND IGG SUBCLASSES IN PATIENTS WITH IGG MYELOMAS
IMMUNITAT UND INFEKTION
Authors: KLOUCHE, M; WILHELM, D; KIRCHNER, H
Abstract
Cytokines play an essential role in normal and malignant B-cell proliferation and isotype-switching. Therefore we determined serum levels of different B-cell activating cytokines including IFN gamma, IL-4 and IL-10, IgG subclasses, further immunoglobulins and the soluble B-cell activation marker sCD23 in 68 patients with recently diagnosed and previously untreated IgG myelomas in comparison with age- and sex-matched healthy controls. Our results demonstrated that 16% of the myeloma patients had elevated IL-10 levels up to 1000 pg/ml and 8% showed increased IFN gamma serum concentrations. By contrast, only 7% of the controls showed detectable IL-10 levels and 3% had measurable IFN gamma levels. While in men 67% of the paraproteins were of the kappa light chain type, we found an equal occurrence of kappa and lambda light chains in women. In addition, the distribution of IgG subclasses differed in men and women. In comparison with the controls, no alteration of sCD23 was detected in myeloma patients. We found an apparent correlation of elevated IL-10 levels and the IgG1 subclass.