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MAdCAM-1 expressing sacral lymph node in the lymphotoxin beta-deficient mouse provides a site for immune generation following vaginal herpes simplex virus-2 infection.

Abstract
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.
AuthorsKelly A Soderberg, Melissa M Linehan, Nancy H Ruddle, Akiko Iwasaki
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 173 Issue 3 Pg. 1908-13 (Aug 01 2004) ISSN: 0022-1767 [Print] United States
PMID15265924 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antibodies, Viral
  • Cell Adhesion Molecules
  • Immunoglobulin G
  • Immunoglobulins
  • LTB protein, human
  • Ltb protein, mouse
  • Lymphotoxin-alpha
  • Lymphotoxin-beta
  • MADCAM1 protein, human
  • Madcam1 protein, mouse
  • Membrane Proteins
  • Mucoproteins
Topics
  • Animals
  • Antibodies, Viral (biosynthesis, immunology)
  • CD4-Positive T-Lymphocytes (immunology)
  • Cell Adhesion Molecules
  • Dendritic Cells (immunology)
  • Female
  • Herpes Genitalis (immunology)
  • Herpesvirus 2, Human (immunology)
  • Immunoglobulin G (biosynthesis, immunology)
  • Immunoglobulins (analysis)
  • Lymph Nodes (chemistry, immunology, pathology)
  • Lymphocyte Activation
  • Lymphotoxin-alpha (deficiency, genetics)
  • Lymphotoxin-beta
  • Membrane Proteins (deficiency, genetics)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mucoproteins (analysis)
  • Sacrococcygeal Region
  • Splenectomy
  • T-Cell Antigen Receptor Specificity
  • Th1 Cells (immunology)
  • Vaginitis (immunology)

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