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.
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.
Soderberg
Kelly A
KA
Department of Epidemiology and Public Health and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Linehan
Melissa M
MM
Ruddle
Nancy H
NH
Iwasaki
Akiko
A
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007136:Immunoglobulins / Q000032:analysis*; D008198:Lymph Nodes / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008233:Lymphotoxin-alpha / Q000172:deficiency* / Q000235:genetics; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009088:Mucoproteins / Q000032:analysis*; D012445:Sacrococcygeal Region; D013156:Splenectomy; D037182:T-Cell Antigen Receptor Specificity; D018417:Th1 Cells / Q000276:immunology; D014627:Vaginitis / Q000276:immunology*
D000914:Antibodies, Viral; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D007136:Immunoglobulins; C505886:LTB protein, human; C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D008565:Membrane Proteins; D009088:Mucoproteins