Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent

Abstract

Atherosclerosis is an inflammatory disease of large arteries. Flow cytometry of aortic cell suspensions showed that B and T lymphocytes and some macrophages and dendritic cells are already present in the adventitia of normal/noninflamed mouse aortas. Adoptively transferred lymphocytes constitutively homed to the aorta and resided within the adventitia up to 7 d after transfer. Lymphocyte trafficking into normal/noninflamed or atherosclerosis-prone aortas was partially L-selectin dependent. Antigen-activated dendritic cells induced increased T lymphocyte proliferation within the aorta 72 h after adoptive transfer. During progression of atherosclerosis in apolipoprotein-E–deficient mice, the total number of macrophages, T cells, and dendritic cells, but not B cells, increased significantly. This alteration in immune cell composition was accompanied by the formation of tertiary lymphoid tissue in the adventitia of atherosclerotic aortas. These results demonstrate that lymphocytes already reside within the normal/noninflamed aorta before the onset atherosclerosis as a consequence of constitutive trafficking. Atherosclerosis induces the recruitment of macrophages and dendritic cells that support antigen presentation.

Characterization of Resident B Cells of Vascular Walls in Human Atherosclerotic Patients

“…In atherosclerosis, lymphocyte infiltration in the adventitia has been known for a long time (35,36), but description of its B cell component is more recent (7)(8)(9)(10)(11)(12)(13). Adoptive transfer experiments showed that vascular wall B lymphocytes constitutively home within arterial regions prone to lesion development (6,7,15,28), indicating a high degree of specialization.…”

“…Adoptive transfer experiments showed that vascular wall B lymphocytes constitutively home within arterial regions prone to lesion development (6,7,15,28), indicating a high degree of specialization. However, many properties of these resident B cells remain to be described.…”

“…B lymphocytes represent a minor component of tunica intima in normal as well as atherosclerotic vessels (7)(8)(9)(10)(11)(12)(13). However, B lymphocytes and plasma cells accumulate in lamina adventitia adjacent to arterial plaques of human patients and of atherosclerosis-prone mice and their numbers generally parallel the severity of vascular lesions (8)(9)(10)(11)(12)(13)(14)(15).…”

“…B cells home in adventitia of normal arteries as the result of a partially L-selectin-dependent physiologic process (7). B lymphocytes represent a minor component of tunica intima in normal as well as atherosclerotic vessels (7)(8)(9)(10)(11)(12)(13).…”

Vascular Stem Cells in Vascular Remodeling and Diseases

“…(67) An early event observed following many forms of arterial injury is adventitial inflammation and an accumulation of monocytes and activated macrophages in the adventitia. (94)(95)(96) This local inflammatory response may be necessary for down-regulation of the ongoing adventitial niche signaling that maintains Sca1 + cells as progenitors, thus resulting in the "release" of these progenitor cells to adopt other cell fates.…”