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© The Rockefeller University Press, 0022-1007/2000/2/435/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 3, February 7, 2000 435-444

Original Article

A Discrete Subpopulation of Dendritic Cells Transports Apoptotic Intestinal Epithelial Cells to T Cell Areas of Mesenteric Lymph Nodes

Fang-Ping Huanga, Nicholas Platta, Michelle Wykesa, James R. Majora, Timothy J. Powella, Christopher D. Jenkinsa, and G. Gordon MacPhersona

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 IIhi, 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

M. Wykes' current address is Mater Medical Research Institute, South Brisbane, Queensland, Australia.

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

Abbreviations used in this paper: aM{Phi}s, 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; pM{Phi}s, 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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