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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 Article has an altmetric score of 6

Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid

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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 2

Kinetics of CCL21-driven entry of splenocytes (spl.

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Kinetics of CCL21-driven entry of splenocytes (spl.
 into the thyroid. G...
into the thyroid. GFP+ splenocytes (107) were injected into RAGTGCCL21 mice. At the indicated time points, thyroids and lymph nodes were analyzed for the presence of GFP+ cells. (A) Few GFP+ cells were found on days 1 and 3 (insets), but their number increased on day 5. Results shown are representative of 80 thyroid sections obtained from 4 mice at each time point. Magnification, ×40 (insets). (B) Splenocytes (107) from GFP-transgenic mice deficient for CCR7 (GFP+/CCR7–/–) were injected into RAGTGCCL21 mice. Ten days later, thyroids and lymph nodes of the recipient mice were extensively analyzed (more than 20 sections/thyroid) for the presence of GFP+ cells. Shown are representative sections (n = 3 mice). (C) All GFP+ cells present on days 1 and 3 in thyroids of RAGTGCCL21 mice stained with anti-CD3 antibody (n = 4 mice in each group). Most GFP+ cells on day 5 are CD3+; however, at this time point, few CD19+ B cells could also be detected (n = 4 mice). Scale bars: 0.05 mm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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