Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid.
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.
Marinkovic
Tatjana
T
Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
Garin
Alexandre
A
Yokota
Yoshifumi
Y
Fu
Yang-Xin
YX
Ruddle
Nancy H
NH
Furtado
Glaucia C
GC
Lira
Sergio A
SA
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*
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