ABSTRACT
This study identifies a dendritic cell (DC) subset that constitutively transports apoptotic intestinal epithelial cell remnants to T cell areas of mesenteric lymph nodes in vivo. Rat intestinal lymph contains two DC populations. Both populations have typical DC morphology, are major histocompatibility complex class II(hi), and express OX62, CD11c, and B7. CD4(+)/OX41(+) DCs are strong antigen-presenting cells (APCs). CD4(-)/OX41(-) DCs are weak APCs and contain cytoplasmic apoptotic DNA, epithelial cell-restricted cytokeratins, and nonspecific esterase (NSE)(+) inclusions, not seen in OX41(+) DCs. Identical patterns of NSE electrophoretic variants exist in CD4(-)/OX41(-) DCs, intestinal epithelial cells, and mesenteric node DCs but not in other DC populations, macrophages, or tissues. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL)-positive DCs and strongly NSE(+) DCs are present in intestinal lamina propria. Peyer's patches and mesenteric but not other lymph nodes contain many strongly NSE(+) DCs in interfollicular and T cell areas. Similar DCs are seen in the ileum and in T cell areas of mesenteric nodes in gnotobiotic rats. These results show that a distinct DC subset constitutively endocytoses and transports apoptotic cells to T cell areas and suggest a role for these DCs in inducing and maintaining peripheral self-tolerance.
Subject(s)
Dendritic Cells/physiology , Epithelial Cells/immunology , Intestines/cytology , Lymph Nodes/physiology , T-Lymphocytes/physiology , Animals , Antigen-Presenting Cells/immunology , Apoptosis/immunology , Cells, Cultured , DNA Fragmentation , Dendritic Cells/immunology , Immune Tolerance , Immunohistochemistry , In Situ Nick-End Labeling , Lymph Node Excision , Lymph Nodes/cytology , Mesentery , Microscopy, Confocal , RatsABSTRACT
It has long been known that tissue dendritic cells (DC) are bone-marrow-derived (1,2). However, early attempts to generate DC from the bone marrow gave only low numbers, presumably because maturation and survival signals required in vivo could not be provided in vitro (3,4). The availability of recombinant cytokines and the observations that DC in culture are dependent on cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) (5,6) and IL-4 (7,8) have revolutionized DC research. This allowed in vitro cultures of bone marrow cells to be supplemented with factors that promoted the maturation and survival of DC precursors into typical DC as judged by phenotype and function. Several years ago Inaba and colleagues reported such a method for murine bone marrow (9). They showed that mouse bone marrow cells depleted of erythrocytes, B cells, and T cells and cultured with recombinant GM-CSF, after 7 d gave rise to cells that were stimulatory in the allogeneic mixed lymphocyte reaction (MLR), the "gold standard" for DC. These cells also expressed typical DC markers such as high MHC class I and MHC class II and other costimulatory molecules. Culture of DC from human bone marrow is possible but more problematic as it is difficult to obtain in large amounts (10-12).
ABSTRACT
Maltase and sucrase activities were measured in the intestine of broilers inoculated with sporulated coccidial oocysts. Infection with Eimeria acervulina, E. maxima, E. necatrix, and E. brunetti decreased disaccharidase activity in the intestinal region in which maximum infection was found compared with the activity in uninoculated controls. The maximum reduction occurred on the first or second day of patency followed by a rapid recovery in activity. Disaccharidase activity was inversely proportional to the inoculum dose.