title: Th1-biased tertiary lymphoid tissue supported by CXC chemokine ligand 13-producing stromal network in chronic lesions of autoimmune gastritis.
abstract: Secondary lymphoid tissue is developmentally programmed and characterized by well-ordered compartmentalization of lymphocyte subsets and specialized stromal cells supporting the tissue architecture. By contrast, tertiary lymphoid tissue is defined as that induced in ectopic sites by inflammation, although its immunological role is largely unknown. In this study, we characterize the lymphoid tissue induced in the chronic lesion of murine autoimmune gastritis (AIG). Within the lymphoid cluster in the gastric mucosa, there is a clear segregation of T and B cells. Follicle-like B cell areas are always located on the luminal side of the mucosa, while T cells are located in the basal part. A typical lymphoid reticular network and follicular dendritic cells support the structure. Importantly, complement receptor 1(+) follicular dendritic cells within the follicle express a B cell homing chemokine, CXC chemokine ligand 13. The number and size of the clusters correlate with the age of the mice and the serum autoantibody titer, suggesting the functional importance of the clusters in local Ab production, although involvement of the autoantibody in the disease progression is still unclear. AIG gastric lesions are known to constitute a Th1-biased, memory T cell-dependent immunomicroenvironment. The expression pattern of cytokines, including lymphotoxin-beta, and chemokines in the AIG stomach is consistent with this observation. Taken together, these facts suggest that, during the chronic phase of autoimmunity, long-lasting lymphocyte infiltration probably induces a unique tertiary lymphoid tissue that has a function distinct from that of regional lymph nodes. These neolymphoid tissues may maintain the local self reactivity supporting the vicious cycle of Th1-type reaction as well as autoantibody production.
authors.affiliation: Center for Molecular Biology and Genetics, Kyoto University, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Katakai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hara
authors.forename: Manabu
authors.initials: M
authors.lastname: Sugai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gonda
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002449:Cell Aggregation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008231:Lymphopenia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis* / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; C099677:CCL13 protein, human; D018925:Chemokines; D016207:Cytokines; D008024:Ligands; D018945:Monocyte Chemoattractant Proteins