Participation of blood vessel cells in human adaptive immune responses

Abstract

Circulating T cells contact blood vessels either when they extravasate across the walls of microvessels into inflamed tissues or when they enter into the walls of larger vessels in inflammatory diseases such as atherosclerosis. The blood vessel wall is largely composed of three cell types: endothelial cells lining the entire vascular tree; pericytes supporting the endothelium of microvessels; and smooth muscle cells forming the bulk of large vessel walls. Each of these cell types interacts with and alters the behavior of infiltrating T cells in different ways, making these cells active participants in the processes of immune-mediated inflammation. In this review, we compare and contrast what is known about the nature of these interactions in humans.

Figure 1

Small and large vessel sites for recruitment of circulating leukocytes. (A) A typical microvessel is composed of a single, continuous layer of endothelial cells supported by an incomplete layer of pericytes. Both cell types are surrounded by a common basement membrane. (B) The wall of a large artery contains a luminal layer of endothelial cells attached to an underlying basement membrane but without the presence of pericytes. The endothelium together with a variable layer of subendothelial connective tissue that may contain phenotypically-modified smooth muscle cells constitutes the vessel intima. The intima is surrounded by the vessel media which consists of concentric layers of densely-packed, concentrically arranged smooth muscle cells separated by elastic laminae. The relatively thick internal elastic lamina marks the boundary between intima and media, whereas the external elastic lamina marks the boundary between media and adventitia. The adventitia contains fibroblasts, vascular stem cells, nerve endings, and, in larger vessels, nutrient microvessels called vasa vasorum. These various constituents of the vessel wall may interact with leukocytes during their trafficking to extravascular sites of inflammation. In the inflamed or atherosclerotic artery, the vasa vasorum may, through the process of angiogenesis, give rise to penetrating microvessels that cross the media and nurture inflammatory cells that accumulate within the intima (not shown).