Lactoferrin targets T cells in the small intestine

Lactoferrin (Lf) belongs to the transferrin family of non-heme iron-binding proteins and is found in milk and mucosal secretions. Consequently, it is now considered a multifunctional protein mainly involved in both the innate and adaptive immune defenses of the organism against various pathogens, and Lf receptors have been identified at the surfaces of a number of different cells. In the small intestine Lf binds to the luminal surface, but its further interaction with the epithelial cells is controversial. In the present work, we studied the uptake of Lf in cultured mucosal explants of pig small intestine by immunofluorescence and immunogold microscopy. Lf rapidly bound to the brush border and subsequently appeared in punctae in the apical cytoplasm, indicating internalization into an endosomal compartment. Essentially, no labeling was detected elsewhere in the enterocytes by 2 h incubation. However, in addition to enterocytes, a distinct subpopulation of cells in the lamina propria also took up Lf, most likely from the serosal side of the explants. None of these cells were apoptotic, nor did they belong to the predominant group of immunoglobulin-synthesizing plasma cells in the lamina propria. However, they were CD3(+), identifying them as T lymphocytes. Lf labeling of these cells was mainly seen in the cytosol, but occasionally nuclear staining was seen as well, suggesting a direct regulatory role of Lf. We propose that Lf functions in the immune defense of the small intestinal mucosa by targeting the population of T cells in the lamina propria.