Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid
Tatjana Marinkovic, … , Glaucia C. Furtado, Sergio A. Lira
Tatjana Marinkovic, … , Glaucia C. Furtado, Sergio A. Lira
Published October 2, 2006
Citation Information: J Clin Invest. 2006;116(10):2622-2632. https://doi.org/10.1172/JCI28993.
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Research Article Immunology

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

Tatjana Marinkovic, Alexandre Garin, Yoshifumi Yokota, Yang-Xin Fu, Nancy H. Ruddle, Glaucia C. Furtado, Sergio A. Lira

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Figure 6

CCR7 is required for the formation of infiltrates.

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CCR7 is required for the formation of infiltrates. GFP+ splenocytes (107...
GFP+ splenocytes (107) were transferred into RAGTGCCL21 mice deficient for CCR7 (RAGTGCCL21/CCR7–/–). (A) Although CCR7 deficiency of the host did not prevent entry of lymphocytes into thyroids, the CD11c+ DC (yellow) clusters observed were small and less frequent. (B) Expression of CXCL9 and CXCL16, chemokines highly upregulated upon entry of T cells in thyroids of RAGTGCCL21 mice, was also impaired in the CCR7-deficient host. Shown are representative sections (n = 4 mice). Scale bars: 0.25 mm.