Atherosclerosis 154 2001 15 – 21
Vascular-associated lymphoid tissue VALT involvement in aortic aneurysm
Yuri V. Bobryshev , Reginald S.A. Lord
Surgical Professorial Unit, Le6el
17
, O
’
Brien Building, St. Vincent
’
s Hospital, Uni6ersity of New South Wales, Darlinghurst, Sydney NSW,
2010
, Australia Received 1 November 1999; accepted 21 February 2000
Abstract
Vascular-associated lymphoid tissue VALT consisting of accumulations of immunocompetent and antigen presenting cells has recently been recognised in the arterial wall. In this study, we investigated the involvement of VALT in immune responses in
abdominal aortic aneurysms AAAs. Tissue samples were collected during operations from 31 patients with atherosclerotic infrarenal abdominal aortic aneurysms ranging in diameters from 5 to 8 cm. The specimens were immediately frozen and
examined using single and double immunohistochemical staining. T-cell subpopulations, B-cells, dendritic cells and macrophages were identified using cell type specific antibodies. Cell contacts were examined by electron microscopy. Most inflammatory
infiltrates were found in the adventitia. T-cells were the predominant cell type in a majority of inflammatory infiltrates but in seventeen cases, typical lymphoid follicles with B-cells forming germinative centres were also observed. In eight cases, the
lymphoid follicles aggregated in lymph node-like structures. Dendritic cells were present within all inflammatory infiltrates and contacted lymphocytes. The present observations show that in aortic aneurysm, VALT is involved in immune responses and its
activation mostly occurs in the adventitia. The formation of lymphoid follicles and lymph node-like structures in the adventitia suggests that VALT might locally serve the entire complex of both cellular and humoral immune responses in the aneurysmal wall.
© 2001 Elsevier Science Ireland Ltd. All rights reserved.
Keywords
:
Abdominal aortic aneurysm AAA; Dendritic cells; Lymphocytes; Inflammation www.elsevier.comlocateatherosclerosis
1. Introduction
Vascular-associated lymphoid tissue VALT consist- ing of disseminated accumulations of immunocom-
petent cells and antigen presenting cells has recently been recognised in the arterial intima [1,2]. In the
non-diseased arterial wall, small numbers of immuno- competent and antigen presenting cells are distributed
throughout the subendothelial layer of the arterial in- tima and some of these cells are also present around the
vasa vasorum in the adventitia [1 – 5]. VALT is proba- bly analogous to mucosa-associated lymphoid tissue
MALT of the respiratory and gastrointestinal tracts and like MALT, VALT probably screens ‘vascular
tissue’ for potentially harmful antigens [1]. Based on the concept of VALT, Wick and co-
workers [1] have proposed a new autoinimune hypo- thesis
for atherogenesis
which postulated
that VALT activation by autoantigens is responsible for
the initiation of immune responses in the arterial wall.
In primary atherosclerosis, immunocompetent cells accumulate within the arterial intima [6 – 9]. In contrast,
in abdominal aortic aneurysms AAAs, there is a dramatic change in the cellular composition of the
outer aortic wall associated with massive infiltration of the external layer of the media and the entire adventitia
by lymphocytes [10 – 12]. Furthermore, in primary atherosclerosis, T-lymphocytes exclusively infiltrate the
intima [6 – 9] while the adventitial infiltrates in AAAs contain large numbers of both T-cells and B-cells
[10 – 12]. Antigen-presenting dendritic cells have also been suggested to accumulate in the media and adventi-
tia of the AAA wall [13].
Corresponding author. Tel.: + 1-617-726-1032; fax: + 1-617-726- 2874.
E-mail address
:
bobryshevmolbio.mgh.harvard.edu Y.V. Bobry- shev.
0021-915001 - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S0021-91500000441-X
During the last decade, the mechanisms responsible for the weakening and destruction of the aortic wall,
which lead to the formation of AAAs, have been intensively studied and the degradation of the extracel-
lular matrix in the medial layer associated with in- creased proteolytic activity have been implicated in the
breakdown of the structural integrity of the aortic wall [14 – 17]. In AAAs, inflammatory cells secrete cytokines
that are the main source of enhanced proteolytic activ- ity responsible for weakening the aortic wall [18].
Despite the significance of immune and inflammatory cells accumulating in the AAA wall, the histopathologi-
cal features of immune inflammation as well as the immunocompetent cell interactions in AAAs have re-
ceived limited attention. We now report the involve- ment of VALT in immune responses in the aortic
aneurysmal wall.
2. Methods
