T cell activation by antigens on human melanoma cells--co-stimulation by B7-1 is neither sufficient nor necessary to stimulate IL-2 secretion by melanoma-specific T cell clones in vitro

International audienceB7-1 expression, Induced by transfectlon in poorly Immunogenic murine tumours, was shown to elicit a T cell-mediated rejection of these tumours and further active immunity against the nontransfected tumour. We therefore asked to what level similarly induced expression of B7 on human melanoma cells would affect the antigen-dependent responses of tumour-speclflc T cell clones In vitro. Data presented show that B7-1 expression by melanoma lines: (I) significantly Induced, or improved, an IL-2-dependent prollferatlve response of such clones to the antigen; (II) Increased the amount of IL-2 produced by two clones In response to the parental non-transfected tumour cells; and (ill) increased the TNF responses of all the CD4 + clones. However, despite these clear co-stimulatory effects on antigen-Induced responses of all T cell clones, which demonstrated an effective interaction of the B7-1 transfected molecule with one or the other of Its counter-receptors expressed on T cell clones, B7 co-stimulation did not correct the defect of IL-2 secretion exhibited by many of these clones in response to In vitro antigen presentation by melanoma cells. We further show that defective IL-2 secretion in response to melanoma antigens was not due to a T cell clone refractoriness induced by the culture, since one of these clones could be Induced to secrete IL-2 by an antigen-expressing melanoma line, upon increased lymphocyte function associated antlgen-3 expression Induced by gene transfectlon. Together these data suggest that defective IL-2 secretion by many tumour-infiltrating lymphocytes clones in response to antigen presentation by melanoma cells In vitro is not exclusively due to the inability of these cells to provide an appropriate co-stimulation through the B7-1 molecule

Neonatal consumption of oligosaccharides greatly increases l-cell density without significant consequence for adult eating behavior.

International audienceOligosaccharides (OS) are commonly added to infant formulas, however, their physiological impact, particularly on adult health programming, is poorly described. In adult animals, OS modify microbiota and stimulate colonic fermentation and enteroendocrine cell (EEC) activity. Since neonatal changes in microbiota and/or EEC density could be long-lasting and EEC-derived peptides do regulate short-term food intake, we hypothesized that neonatal OS consumption could modulate early EECs, with possible consequences for adult eating behavior. Suckling rats were supplemented with fructo-oligosaccharides (FOS), beta-galacto-oligosaccharides/inulin (GOS/In) mix, alpha-galacto-oligosaccharides (αGOS) at 3.2 g/kg, or a control solution (CTL) between postnatal day (PND) 5 and 14/15. Pups were either sacrificed at PND14/15 or weaned at PND21 onto standard chow. The effects on both microbiota and EEC were characterized at PND14/15, and eating behavior at adulthood. Very early OS supplementation drastically impacted the intestinal environment, endocrine lineage proliferation/differentiation particularly in the ileum, and the density of GLP-1 cells and production of satiety-related peptides (GLP-1 and PYY) in the neonatal period. However, it failed to induce any significant lasting changes on intestinal microbiota, enteropeptide secretion or eating behavior later in life. Overall, the results did not demonstrate any OS programming effect on satiety peptides secreted by L-cells or on food consumption, an observation which is a reassuring outlook from a human perspective

Neonatal Consumption of Oligosaccharides Greatly Increases L-Cell Density without Significant Consequence for Adult Eating Behavior

International audienceOligosaccharides (OS) are commonly added to infant formulas, however, their physiological impact, particularly on adult health programming, is poorly described. In adult animals, OS modify microbiota and stimulate colonic fermentation and enteroendocrine cell (EEC) activity. Since neonatal changes in microbiota and/or EEC density could be long-lasting and EEC-derived peptides do regulate short-term food intake, we hypothesized that neonatal OS consumption could modulate early EECs, with possible consequences for adult eating behavior. Suckling rats were supplemented with FOS, GOS/inulin mix, αGOS (3.2 g/kg), or a control solution between postnatal day (PND) 5 and 14/15. Pups were either sacrificed at PND14/15 or weaned at PND21 onto standard chow. The effects on both microbiota and EEC were characterized at PND14/15, and eating behavior at adulthood. Very early OS supplementation drastically impacted the intestinal environment, endocrine lineage proliferation/differentiation particularly in the ileum, and the density of GLP-1 cells and production of satiety-related peptides (GLP-1 and PYY) in the neonatal period. However, it failed to induce any significant lasting changes on intestinal microbiota, enteropeptide secretion or eating behavior later in life. Overall, the results did not demonstrate any OS programming effect on satiety peptides secreted by L-cells or on food consumption, an observation which is a reassuring outlook from a human perspective