From Bystander to Commander

Atherosclerosis, the principal pathology underlying most cardiovascular disease, is characterized by a prominent infiltration of inflammatory cells into the vessel wall.1–3 Whereas most research traditionally focused on the inflammatory reaction in the intima of the vessel, the adventitia has not attracted much attention as an immune-active site. Recently, however, several experimental studies have demonstrated sparse distribution of leukocytes in the adventitia of healthy arteries4 and massive accumulations of inflammatory cells around atherosclerotic vessels.5 These conglomerates, observed preferentially around athero-prone areas of the vessel and termed vascular-associated lymphoid tissues (VALTs),6 contain T and B lymphocytes, dendritic cells, and lymphoid tissue inducer cells. Although the adventitia of nondiseased arteries contains a network of microvessels, termed vasa vasorum, VALTs are characterized by an extensive degree of neovascularization. Accordingly, Galkina et al7 demonstrated that recruitment of lymphocytes to advanced atherosclerotic lesions is mainly mediated via this nonluminal site. In contrast, in early stages of atherosclerosis, leukocyte recruitment is facilitated through the luminal surface because the intimal and adventitial sites of …