The Journal of Experimental Medicine
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Published 5 May 2003. doi:10.1084/jem.20021761
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© Rockefeller University Press, 0022-1007/2003/5/1153 $5.00
The Journal of Experimental Medicine, Volume 197, Number 9, 1153-1163

Ectopic LT{alpha}ß Directs Lymphoid Organ Neogenesis with Concomitant Expression of Peripheral Node Addressin and a HEV-restricted Sulfotransferase

Danielle L. Drayton, Xiaoyan Ying, Jason Lee, Werner Lesslauer and Nancy H. Ruddle

Department of Epidemiology and Public Health and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520

Address correspondence to Nancy H. Ruddle, Yale University School of Medicine, Department of Epidemiology and Public Health, 60 College St., P.O. Box 208034, New Haven, CT 06520-8034. Phone: 203-785-2915; Fax: 203-785-6130; E-mail: nancy.ruddle{at}yale.edu

Lymph node (LN) function depends on T and B cell compartmentalization, antigen presenting cells, and high endothelial venules (HEVs) expressing mucosal addressin cell adhesion molecule (MAdCAM-1) and peripheral node addressin (PNAd), ligands for naive cell entrance into LNs. Luminal PNAd expression requires a HEV-restricted sulfotransferase (HEC-6ST). To investigate LT{alpha}ß's activities in lymphoid organogenesis, mice simultaneously expressing LT{alpha} and LTß under rat insulin promoter II (RIP) control were compared with RIPLT{alpha} mice in a model of lymphoid neogenesis and with LTß-/- mice. RIPLT{alpha}ß pancreata exhibited massive intra-islet mononuclear infiltrates that differed from the more sparse peri-islet cell accumulations in RIPLT{alpha} pancreata: separation into T and B cell areas was more distinct with prominent FDC networks, expression of lymphoid chemokines (CCL21, CCL19, and CXCL13) was more intense, and L-selectin+ cells were more frequent. In contrast to the predominant abluminal PNAd pattern of HEV in LTß-/- MLN and RIPLT{alpha} pancreatic infiltrates, PNAd was expressed at the luminal and abluminal aspects of HEV in wild-type LN and in RIPLT{alpha}ß pancreata, coincident with HEC-6ST. These data highlight distinct roles of LT{alpha} and LT{alpha}ß in lymphoid organogenesis supporting the notion that HEC-6ST–dependent luminal PNAd is under regulation by LT{alpha}ß.

Key Words: lymphoid organogenesis • chemokines • sulfotransferase • inflammation • high endothelial venules


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