High endothelial venules

Abstract

Secondary lymphoid organs, including peripheral lymph nodes (PLNs), mesenteric lymph nodes (MLNs), Peyer’s patches (PPs), appendix, tonsils, and spleen are essential components of the immune system. These organs are specialized to collect antigen (Ag) and Ag presenting cells (APCs) from distinct anatomical regions. Their extravascular environment is designed to optimize lymphocyte recognition of and subsequent responses to cognate Ag. A remarkable property of secondary lymphoid organs is their ability to recruit vast numbers of circulating B and T lymphocytes. With the exception of the spleen, secondary lymphoid organs contain specialized post-capillary and small collecting venules, called high endothelial venules (HEVs), which serve as the principal site of lymphocyte entry from the blood (1,2). High endothelial venules express organ-specific patterns of lymphocyte traffic molecules that are not found in other microvascular beds. These molecules coordinate the recruitment of circulating lymphocytes by promoting multi-step adhesion cascades involving selectins, chemokines, integrins, and their respective ligands (3,4). In this chapter, we will review our current understanding of the functional, structural, and molecular characteristics of HEVs that allow them to function as the gateway to secondary lymphoid organs. We will examine the development of HEVs in normal and pathologic settings and how these unique microvessels respond to environmental cues. In addition, we will discuss techniques to study these structures as well as emerging technologies that may pave the way for future discoveries.