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 7

CD3+CD4+ T cells induce formation of PNAd+ vessels in thyroids of RAGTGCCL21 mice.

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CD3+CD4+ T cells induce formation of PNAd+ vessels in thyroids of RAGTGC...
(A) GFP+CD3+CD4+ T cells (1 × 106) were injected i.v. into RAGTGCCL21 mice. Mice were sacrificed 10 days later, and thyroids were analyzed for the presence of GFP+ cells and PNAd+ vessels. PNAd+ vessels were not present in thyroids of RAGTGCCL21 mice prior to injection (inset) but were readily visualized (red) in thyroids of all mice injected with GFP+CD3+CD4+ T cells (n > 50 mice). In all cases, formation of PNAd+ structures was accompanied by the clustering of CD11c+ DCs (blue). (B) RAGTGCCL21/CCR7–/– mice were injected with 1 × 107 GFP+ splenocytes. One month after transfer, mice were sacrificed and thyroids analyzed for the presence of PNAd+ vessels. No PNAd+ vessels were observed in sections from CCR7-deficient recipients (>240 sections obtained from 8 mice). PNAd+ HEVs were readily detected in lymph nodes. Representative sections are presented. Scale bars: 0.05 mm.