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Original Article

^a Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
Sir William Dunn School of Pathology, South Parks Rd., Oxford OX1 3RE, UK.44-1865-27550144-1865-275584

gordon.macpherson{at}path.ox.ac.uk

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.

Key Words: rat • lymph • esterase • self tolerance • oral tolerance

T.J. Powell's current address is Institute for Animal Health, Compton, Berks, UK.

Abbreviations used in this paper: aMs, alveolar macrophages; CLN, cervical lymph node; DCs, dendritic cells; IECs, intestinal epithelial cells; L-DC, lymph-borne dendritic cell; LP, lamina propria; MLNs, mesenteric lymph nodes; NSE, nonspecific esterase; pMs, peritoneal macrophages; PP, Peyer's patch; SPF, specific pathogen–free; TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick-end labeling.

© 2000 The Rockefeller University Press

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This article has been cited by other articles:

• Kushwah, R., Oliver, J. R., Zhang, J., Siminovitch, K. A., Hu, J. (2009). Apoptotic Dendritic Cells Induce Tolerance in Mice through Suppression of Dendritic Cell Maturation and Induction of Antigen-Specific Regulatory T Cells. J. Immunol. 183: 7104-7118 [Abstract] [Full Text]  
• Roncarolo, M.-G., Levings, M. K., Traversari, C. (2001). Differentiation of T Regulatory Cells by Immature Dendritic Cells. JEM 193: f5-f10 [Full Text]  
• Steinman, R. M., Turley, S., Mellman, I., Inaba, K. (2000). The Induction of Tolerance by Dendritic Cells That Have Captured Apoptotic Cells. JEM 191: 411-416 [Full Text]  

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