title: Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid.
abstract: Ectopic expression of CC chemokine ligand 21 (CCL21) in the thyroid leads to development of lymphoid structures that resemble those observed in Hashimoto thyroiditis. Deletion of the inhibitor of differentiation 2 (Id2) gene, essential for generation of CD3-CD4+ lymphoid tissue-inducer (LTi) cells and development of secondary lymphoid organs, did not affect formation of tertiary lymphoid structures. Rather, mature CD3+CD4+ T cells were critical for the development of tertiary lymphoid structures. The initial stages of this process involved interaction of CD3+CD4+ T cells with DCs, the appearance of peripheral-node addressin-positive (PNAd+) vessels, and production of chemokines that recruit lymphocytes and DCs. These findings indicate that the formation of tertiary lymphoid structures does not require Id2-dependent conventional LTis but depends on a program initiated by mature CD3+CD4+ T cells.
authors.affiliation: Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Marinkovic
authors.forename: Alexandre
authors.initials: A
authors.lastname: Garin
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Yokota
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Ruddle
authors.forename: Glaucia C
authors.initials: GC
authors.lastname: Furtado
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lira
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D054421:Chemokine CCL21; D018925:Chemokines / Q000235:genetics; D019742:Chemokines, CC / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression / Q000276:immunology; D049452:Green Fluorescent Proteins / Q000235:genetics; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008233:Lymphotoxin-alpha / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics; D013959:Thyroid Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology*
chemical_list: D017252:CD3 Complex; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D015815:Cell Adhesion Molecules; D054421:Chemokine CCL21; D018925:Chemokines; D019742:Chemokines, CC; D004268:DNA-Binding Proteins; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; C499308:Rag2 protein, mouse; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C084881:flt3 ligand protein; D049452:Green Fluorescent Proteins