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Cytokines can be functionally active across species barriers. Bovine IL-10 has an amino acid sequence identity with human IL-10 of 76.8%. Therefore, the aim of this study was to evaluate whether bovine IL-10 has immunomodulatory activities on human monocytes and dendritic cells. Peripheral blood monocytes were isolated from healthy donors, and used directly or allowed to differentiate to dendritic cells under the influence of IL-4 and GM-CSF. Recombinant bovine IL-10 inhibited TLR induced activation of monocytes, and dose-dependently inhibited LPS-induced activation of monocyte-derived DCs comparable to human IL-10. By using blocking antibodies to either bovine IL-10 or the human IL-10 receptor it was demonstrated that inhibition of monocyte activation by bovine IL-10 was dependent on binding of bovine IL-10 to the human IL-10R. These data demonstrate that bovine IL-10 potently inhibits the activation of human myeloid cells in response to TLR activation. Bovine IL-10 present in dairy products may thus potentially contribute to the prevention of necrotizing enterocolitis and allergy, enhance mucosal tolerance induction and decrease intestinal inflammation and may therefore be applicable in infant foods and in immunomodulatory diets. [ABSTRACT FROM AUTHOR]

The interaction between CD28 on T cells with CD80 (B7-1) and CD86 (B7-2) on APCs is considered to be of critical importance for primary T cell activation both in vivo and in vitro. The relative importance of this co-stimulatory signal in memory T cell activation is, however, less clear, and was therefore studied by in vitro experiments on T cell responses to soluble recall antigens using peripheral blood mononuclear cells or T cell clones. Our data demonstrate that B7-2 represents the major co-stimulatory signal for the activation of resting peripheral blood memory T cells with recall antigens, as evidenced by the effects of anti-B7-1 and anti-B7-2 on T cell proliferation as well as on IL-2 and INF-y production. Since CTLA-4-lg and anti-CD28 Fab fragments had similar inhibitory effects to the combination of anti-B7-1 plus anti-B7-2, the involvement of a third co-stimulatory CD28/CTLA-4 ligand is unlikely. Despite the strong effects of B7-blocking agents, a variable fraction of the memory T cells was resistant to inhibition. Moreover, T cell clones or in vitro preactivated T cells could efficiently be restimulated by soluble antigens on autologous APCs in the absence of B7-1 or B7-2 co-stimulation. These data show that most memory T cells that are freshly isolated from the blood are still dependent on CD28 triggering for their activation. However, recently activated T cells can apparently bypass the requirement for B7 and use other co-stimulatory signals for reactivation, a finding with important implications for the development of immunosuppressive strategies. [ABSTRACT FROM AUTHOR]

Bovine immunoglobulin G (bIgG) was previously shown to enhance innate immune responses to toll-like receptor (TLR) stimulation, via induction of trained immunity. In this study, we investigated whether minimally processed dairy streams with high levels of whey proteins as potential infant nutrition ingredients could also induce trained immunity, and to what extent this can be explained by the presence of bIgG. The minimally processed whey ingredients serum protein concentrate (SPC) and whey protein concentrate (WPC) were tested for their ability to induce trained immunity in human peripheral blood monocytes. Both ingredients induced trained immunity as evidenced by an increased production of TNF-α and, to a lesser extent, of IL-6 upon stimulation with TLR ligands. This was comparable to isolated bovine immunoglobulin G (bIgG) that served as positive control. Depletion of bIgG from both whey protein-containing ingredients did not significantly inhibit the induction of trained immunity, suggesting that the streams contain other components in addition to bIgG that are able to induce trained immunity. These results indicate that minimally processed whey ingredients may contribute to protection against infections through enhancing innate immune responsiveness to pathogens.