Follicular dendritic cells, conduits, lymphatic vessels, and high endothelial venules in tertiary lymphoid organs: Parallels with lymph node stroma

Abstract

In this communication, the contribution of stromal, or non-hematopoietic, cells to the structure and function of lymph nodes (LNs), as canonical secondary lymphoid organs (SLOs), is compared to that of tertiary lymphoid tissue or organs (TLOs), also known as ectopic lymphoid tissues. TLOs can arise in non-lymphoid organs during chronic inflammation, as a result of autoimmune responses, graft rejection, atherosclerosis, microbial infection, and cancer. The stromal components found in SLOs including follicular dendritic cells, fibroblast reticular cells, lymphatic vessels, and high endothelial venules and possibly conduits are present in TLOs; their molecular regulation mimics that of LNs. Advances in visualization techniques and the development of transgenic mice that permit in vivo real time imaging of these structures will facilitate elucidation of their precise functions in the context of chronic inflammation. A clearer understanding of the inflammatory signals that drive non-lymphoid stromal cells to reorganize into TLO should allow the design of therapeutic interventions to impede the progression of autoimmune activity, or alternatively, to enhance anti-tumor responses.

Keywords: autoimmunity; cancer; chronic inflammation; secondary lymphoid organ; tertiary lymphoid tissue.

FIGURE 1

A comparison of a lymph node with a TLO, a salivary gland from an individual with Sjögren’s syndrome. Note that the HEVs and lymphatic vessels are colored to indicate the existence of mice with green fluorescent HEVs (Bentley et al., 2011) and red fluorescent lymphatic vessels (Truman et al., 2012) that have been developed to facilitate in vivo imaging.

FIGURE 2

Presumptive conduit in a RIPLTα TLO. Infiltrate of a RIPLTα mouse with a kidney infiltrate, stained with ER-TR7 (red; A) anti-CD3 (green; B). Note the presence of the fine network of ER-TR7⁺ cells underlying the infiltrate.