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 8

LTβR signaling regulates formation of PNAd+ structures in the thyroid.

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LTβR signaling regulates formation of PNAd+ structures in the thyroid. ...
GFP+CD4+ T cells (106) were injected i.v. into RAGTGCCL21 mice. At days 1, 3, 5, and 7, mice were injected i.v. with 100 μg (400 μg total) of LTβR-IgG fusion protein. The control group was treated with mouse IgG. At day 10, mice were sacrificed and thyroids and lymph nodes analyzed for the presence of PNAd+ vessels. (A) PNAd+ vessels were readily detected in thyroids of all control mice (n = 6). In contrast, no PNAd+ cells were detected in thyroid sections (>800 sections from n = 8 mice) of animals treated with LTβR-IgG fusion protein. Inset shows a higher magnification (×40) of a PNAd+ vessel surrounded by GFP+ cells. (B) Expression of ICAM and VCAM was not affected by LTβR-IgG treatment. (C) PNAd+ vessels present in thyroids of TGCCL21 and TGCCL21/LTα–/– mice were analyzed for the expression of HEC-6ST, a marker of mature HEVs. PNAd+ vessels in thyroids of TGCCL21/LTα–/– mice had flat endothelia and did not express HEC-6ST, suggesting that they were not fully developed HEVs. Scale bars: 0.05 mm.