CD8+ T-cell subpopulations in human abdominal aortic aneurysm lesion.

Abdominal Aortic Aneurysm Lesion To the Editor: We read with interest the article by Duftner et al1 reporting the prevalence of peripheral interferon(IFN)–producing CD4 CD28 and CD8 CD28 T cells in patients with small abdominal aortic aneurysm (AAA). Along with the recent description that Th1-type immune responses predominate in human end-stage AAA lesion,2,3 their observation further supports preference toward polarized type 1 T-cell responses in aneurysm disease. The potential involvement of Th1 cells in the pathogenesis of the disorder is also suggested by the convincing demonstration that absence of CD4 T cells or targeted deletion of IFNprevents the induction of experimental AAA in a calcium chloride–induced mouse model,4 AAA formation being reconstituted by administration of IFNinto CD4 / mice or infusion of competent splenocytes from wild-type mice into IFN/ mice. In their study, Duftner et al further established that both circulating CD4 CD28 and CD8 CD28 T cells are highly differentiated cells that display extensive CD45RO to CD45RA reversion and produce large amounts of IFNand perforin. Surprisingly, low percentages of CD8 CD28 T cells were identified in AAA tissue sections using immunohistochemistry compared with flow cytometric analysis of peripheral blood mononuclear cells. In a series of our own, we examined the surface phenotype of infiltrating T lymphocytes freshly isolated from aneurysmal aortic wall for comparison with their circulating counterparts using flow cytometry. As shown in the Table, ex vivo immunophenotyping confirmed reduced proportions of CD8 CD28 T cells in the aneurysmal aortic wall compared with control peripheral blood. In view of the regulatory properties of CD8 CD28 T cells,5,6 their decrease in human AAA wall might suggest their potential implication in the regulation of aortic wall immune responses. This underscores the need for future studies to assess the presence of and delineate the role played by various regulatory T-cell subsets in aneurysm disease. Besides, a population of CD8 T cells lacking the costimulatory molecule CD27 was detected in human AAA lesion compared with control peripheral blood (Table). Focusing on the distribution of CD8 T-cell subsets in AAA specimens, we observed for the first time local expansion of CD8 CD27 cells compared with CD8 CD28 cells (Table). Furthermore, the proportion of infiltrating CD45RO T cells was higher among the CD8 CD27 subset (median percentage of positive cells 70%; minimum value 57, maximum value 86) than the CD8 CD28 subset (median percentage of positive cells 44%; minimum value 43; maximum value 45). Although preliminary, our data suggest the presence of both intermediate and late differentiated7 CD8 T-cell subsets in human end-stage AAA lesion. Moreover, because CD27 is a key determinant for the accumulation of CD8 effector T cells at tissue sites,8,9 our findings highlight the possibility that lesional CD8 CD27 T cells could participate in the regulation of the expansion and maintenance of CD8 effector T-cell subpopulations in the aortic wall. Further experimental studies are needed to reveal the exact role of the differentiation process in aortic wall immune responses and to clarify the functional relevance of distinct subsets of CD8 T cells with differing functional and migratory properties.