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The Journal of Immunology, 2004, 173: 1908-1913.
Copyright © 2004 by The American Association of Immunologists

MAdCAM-1 Expressing Sacral Lymph Node in the Lymphotoxin {beta}-Deficient Mouse Provides a Site for Immune Generation Following Vaginal Herpes Simplex Virus-2 Infection1

Kelly A. Soderberg, Melissa M. Linehan, Nancy H. Ruddle and Akiko Iwasaki2

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

The members of the lymphotoxin (LT) family of molecules play a critical role in lymphoid organogenesis. Whereas LT{alpha}-deficient mice lack all lymph nodes and Peyer’s patches, mice deficient in LT{beta} retain mesenteric lymph nodes and cervical lymph nodes, suggesting that an LT{beta}-independent pathway exists for the generation of mucosal lymph nodes. In this study, we describe the presence of a lymph node in LT{beta}-deficient mice responsible for draining the genital mucosa. In the majority of LT{beta}-deficient mice, a lymph node was found near the iliac artery, slightly misplaced from the site of the sacral lymph node in wild-type mice. The sacral lymph node of the LT{beta}-deficient mice, as well as that of the wild-type mice, expressed the mucosal addressin cell adhesion molecule-1 similar to the mesenteric lymph node. Following intravaginal infection with HSV type 2, activated dendritic cells capable of stimulating a Th1 response were found in this sacral lymph node. Furthermore, normal HSV-2-specific IgG responses were generated in the LT{beta}-deficient mice following intravaginal HSV-2 infection even in the absence of the spleen. Therefore, an LT{beta}-independent pathway exists for the development of a lymph node associated with the genital mucosa, and such a lymph node serves to generate potent immune responses against viral challenge.




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