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 4

CD3+CD4+ T cell infiltration induces clustering of DCs and expression of adhesion molecules in the thyroid.

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CD3+CD4+ T cell infiltration induces clustering of DCs and expression of...
GFP+CD3+CD4+ T cells (106) were injected i.v. into RAGTGCCL21 mice. (A) Thyroids from mice sacrificed on days 3 and 10 were stained with anti-CD11c antibody for visualization of DCs. Inset shows higher magnification (×40) of the DC/T cell cluster present on day 3 after T cell transfer. (B) Double staining for CD11c (red) with ICAM (blue) or VCAM (blue) on day 10 revealed that adhesion molecules were expressed by DCs (magenta). Notice expression of VCAM on vessel cells as well as on host CD11c– cells. Shown are representative sections (n = 3 mice at each time point). (C) CD3+CD4+ T cells (1 × 106) were injected i.v. into RAGTGCCL21 mice. At day 5, mice were injected again with 1 × 106 CD11c+ cells sorted from the bone marrow of mice double transgenic for Flt3 ligand and GFP. As a control, GFP+ DCs alone were injected into RAG and RAGTGCCL21 mice. After 5 days, thyroids of recipient mice (n = 2 in each group) were analyzed for the presence of GFP+ cells. Representative sections are presented. Scale bars: 0.05 mm.