Helicobacter-induced chronic active lymphoid aggregates have characteristics of tertiary lymphoid tissue - PubMed (original) (raw)

Helicobacter-induced chronic active lymphoid aggregates have characteristics of tertiary lymphoid tissue

Nirah H Shomer et al. Infect Immun. 2003 Jun.

Abstract

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.

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Figures

FIG. 1.

FIG. 1.

Formation of lymphoid tissue in Helicobacter sp.-infected mouse livers. (A) Hematoxylin and eosin photomicrograph of a typical inflammatory infiltrate at 24 weeks postinfection. (B-C) Serial sections of mouse liver (7 weeks postinfection) stained for CD3-positive T cells (B) and B220-positive B cells (C). Clusters of CD3+ T cells are present, and B220 staining shows B-cell clusters colocalizing with, but separate from, T-cell clusters. (D) VCAM: dark red diffuse staining is visible in areas of intense inflammatory infiltrate (7 weeks postinfection). (E-F) Blood vessels develop a morphology resembling HEV and express MAdCAM-1 (E) and PNAd (F) (7 weeks postinfection). (G-H) In situ hybridization analysis of SLC mRNA expression mouse livers using DIG-labeled RNA probes. (G) Expression of SLC is indicated by purple staining of cells with SLC-antisense probes. (H) No staining is seen with SLC sense probe. Infiltrating cells are counterstained with methyl green. (I-J) In situ hybridization analysis of BLC mRNA expression mouse livers using DIG-labeled RNA probes. (I) Expression of BLC is indicated by purple staining of cells with BLC-antisense probes. (J) No staining is seen with BLC sense probe. Infiltrating cells are counterstained with methyl green.

FIG. 2.

FIG. 2.

FACS analysis of mononuclear cells from liver infiltrates (results shown are the means of results of three experiments). (A) Cells isolated from infected and uninfected mice at 24 weeks postinoculation were labeled with Mac-1, CD4, CD8, and B220. Infected livers had quantitatively more cells than livers from uninfected controls. (B) Cells were gated for naïve T cells (low CD44 expression), and numbers of LPAM- or CD62L-positive cells are shown in the bottom right quadrant of each panel. L-selectin-positive cells, but not LPAM-positive cells, were actively recruited to the livers of infected mice.

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