Helicobacter-induced chronic active lymphoid aggregates have characteristics of tertiary lymphoid tissue.
Susceptible strains of mice that are naturally or experimentally infected with murine intestinal helicobacter species develop hepatic inflammatory lesions that have previously been described as chronic active hepatitis. The inflammatory infiltrates in some models of chronic autoimmunity or inflammation resemble tertiary lymphoid organs hypothesized to arise by a process termed lymphoid organ neogenesis. To determine whether hepatic inflammation caused by infection with helicobacter could give rise to tertiary lymphoid organs, we used fluorescence-activated cell sorting, immunohistochemistry, and in situ hybridization techniques to identify specific components characteristic of lymphoid organs in liver tissue sections and liver cell suspensions from helicobacter-infected mice. Small venules (high endothelial venules [HEVs]) in inflammatory lesions in Helicobacter species-infected livers were positive for peripheral node addressin. Mucosal addressin cell adhesion molecule also stained HEVs and cells with a staining pattern consistent with scattered stromal cells. The chemokines SLC (CCL 21) and BLC (CXCL13) were present, as were B220-positive B cells and T cells. The latter included a naïve (CD45lo-CD62Lhi) population. These findings suggest that helicobacter-induced chronic active hepatitis arises through the process of lymphoid organ neogenesis.
Shomer
Nirah H
NH
Section of Comparative Medicine, Yale University, New Haven, Connecticut 06510, USA. nirah@bu.edu
Fox
James G
JG
Juedes
Amy E
AE
Ruddle
Nancy H
NH
D000818:Animals; D017951:Antigen Presentation; D000954:Antigens, Surface / Q000032:analysis; D015551:Autoimmunity; D015815:Cell Adhesion Molecules; D002449:Cell Aggregation; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000235:genetics; D019743:Chemokines, CXC / Q000235:genetics; D016481:Helicobacter Infections / Q000276:immunology* / Q000473:pathology; D006521:Hepatitis, Chronic / Q000276:immunology* / Q000473:pathology; D007136:Immunoglobulins / Q000032:analysis; D008099:Liver / Q000473:pathology; D008221:Lymphoid Tissue / Q000473:pathology*; D008565:Membrane Proteins; D051379:Mice; D009088:Mucoproteins / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D000954:Antigens, Surface; C515479:Ccl21c protein, mouse; D015815:Cell Adhesion Molecules; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D007136:Immunoglobulins; C069886:L-selectin counter-receptors; C489082:Madcam1 protein, mouse; D008565:Membrane Proteins; D009088:Mucoproteins; D019010:Vascular Cell Adhesion Molecule-1