Transforming growth factor-β1 enhances IgG and IgA sheep red blood cell responses

Abstract

Antibody responses to ingested antigens can be inhibited by a mechanism known as oral tolerance which acts to prevent excessive stimulation from luminal contents. Local IgA responses can be induced in this non-responsive environment and during intestinal inflammation, mucosal IgG responses can also be increased. The purpose of this study was to compare a panel of cytokines to factors from macrophage-T cell co-culture supernatants for their ability to enhance isotype and sheep red blood cell (SRBC)-specific plaque-forming cell responses in an in vitro model of oral tolerance. IL-2, IL-4, IL-5, and IL-6, which have been implicated in IgA regulation of lipopolysaccharide-stimulated B cells, were not capable of enhancing responses in tolerized cultures; however, transforming growth factor (TGF)-beta 1 had a dose-dependent ability to enhance responses to the T cell-dependent antigen SRBCs in this system. The enhancement was only seen when antigen was present and was neutralized by specific rabbit antiserum but not normal rabbit IgG. Similar treatment of soluble factors from the macrophage-T cell co-cultures did not inhibit their ability to enhance responses suggesting at least two distinct molecular mechanisms could augment responses in tolerized cultures. This was substantiated further by showing that TGF-beta 1 was not isotype-specific. In contrast, adsorption of the macrophage-T cell co-culture supernatants against monoclonal IgA or IgG removed isotype-specific binding factors which were necessary for the enhancement of IgA and IgG respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The Inhibitory Effects of Transforming Growth Factor-Beta-1 (TGF-β1) in Autoimmune Diseases

“…TGF-1 can also enhance the growth of naive T cells [133], and influence the differentiation of dendritic cells [134]. In addition, TGF-1 serves as a switch factor for IgA, and in co-operation with IL-2 and IL-5, it upregulates IgA secretion by activated B lymphocytes [135][136][137]. This emphasizes the importance of this cytokine in mucosal immunity.…”

Staphylococcal Enterotoxin B Stimulates Expansion of Autoreactive T Cells That Induce Apoptosis in Intestinal Epithelial Cells: Regulation of Autoreactive Responses by IL-10

“…Single-cell preparations were made by mincing spleen and lysing RBC in ammoniun chloride (0.15 M), potassium carborate (1 nM), and EDTA (0.1 nM) buffer (pH 7.3) lysing buffer; using standard techniques (27). Colonic mucosal T cells were isolated using a modification of a previously described procedure (28).…”

“…The IL-2 concentration of culture supernatant was detected by bioassay using the CTLL-2 hybridoma (27). Cells (5000/50 l medium) were incubated with 50 l of samples or standards (recombinant human IL-2, Genzyme, Cambridge, MA) in triplicate for 24 h. [ 3 H]thymidine (1 Ci/ well) was added during the last 8 h of incubation, and [ 3 H]thymidine incorporation was detected as described above.…”