Lymphatic vessels and tertiary lymphoid organs

Abstract

Tertiary lymphoid organs (TLOs) are accumulations of lymphoid cells in chronic inflammation that resemble LNs in their cellular content and organization, high endothelial venules, and lymphatic vessels (LVs). Although acute inflammation can result in defective LVs, TLO LVs appear to function normally in that they drain fluid and transport cells that respond to chemokines and sphingosine-1-phosphate (S1P) gradients. Molecular regulation of TLO LVs differs from lymphangiogenesis in ontogeny with a dependence on cytokines and hematopoietic cells. Ongoing work to elucidate the function and molecular regulation of LVs in TLOs is providing insight into therapies for conditions as diverse as lymphedema, autoimmunity, and cancer.

Figure 1. Comparison of a LN and a salivary gland TLO.

Note the presence in both of T and B cell organization, APCs, stromal cells, conduits, chemokines, HEVs, and LVs. One difference is the apparent absence of a capsule in the TLO compared with the LN. Another possible difference concerns uncertainty regarding whether the TLO LVs are afferent and/or efferent. FDC, follicular DC.

Figure 2. Diagrammatic rendering of actual staining of a TLO from a mouse salivary gland.

(A) Giemsa staining of TLO reveals the presence of leukocytes. (B) Staining for B cells (B220, green) and T cells (CD3, red). (C) Staining for HEVs (MECA 79, red) and LVs (LYVE1, green). Note that the LVs are filled with lymphocytes, which indicates that transport of these cells is occurring and, thus, suggests that these LVs possess afferent and/or efferent function. Adapted from Proceedings of the National Academy of Sciences of the United States of America (36); copyright (2007) National Academy of Sciences, USA.