Cécile Galle

Predominance of type 1 CD4+T cells in human abdominal aortic aneurysm

The functional repertoire of T cells in abdominal aortic aneurysm (AAA) and the exact nature of aortic wall adaptive cellular immune responses still remains a matter of debate. In this study, we sought to determine whether type 1 or type 2 responses occur predominantly in human aneurysmal aortic lesions. We first examined the phenotype and cytokine secretion profile of T lymphocytes freshly isolated from aneurysmal aortic wall for comparison with their circulating counterparts using flow cytometry. We found that both populations of infiltrating CD4+ and CD8+T cells displayed a unique activated memory phenotype. In addition, we identified the presence in human aneurysmal aortic lesion of CD4+T cells producing high levels of interferon (IFN)‐γ but not interleukin (IL)‐4, reflecting their type 1 nature. Quantitative analysis of cytokine gene expression confirmed increased IFN‐γ transcript levels in infiltrating cells compared to controls. We next analysed aortic wall responses using LightCycler‐based quantitative real‐time reverse transcription‐polymerase chain reaction. Compared to control non‐diseased aortic samples, we demonstrated that whole AAA tissues exhibited high mRNA levels of IFN‐γ but not IL‐4. Overexpression of the transcription factor T‐bet in the absence of significant GATA‐3 expression further assessed the type 1 polarization of aortic wall immune responses. These findings indicate that type 1 CD4+T cells predominate in human AAA lesions. This study has important implications for the pathogenesis of aneurysm disease. Through the production of IFN‐γ, T cells may indeed contribute to orchestrate extracellular matrix remodelling.

Monocyte CD40 expression in severe sepsis.

CD40 is a cell surface protein belonging to the tumor necrosis factor (TNF) receptor family. Ligation of monocyte CD40 by the T cell-derived CD40 ligand can trigger the production of various mediators, the transcription and activation of enzymes, and the upregulation of costimulatory molecules involved in the pathogenesis of sepsis. To test the hypothesis that CD40 is expressed on the surface of monocytes during sepsis, we measured CD40 expression by flow cytometry on freshly sampled monocytes from 40 patients with severe sepsis, including 15 patients with bacteremia, and from eight healthy volunteers. Plasma concentrations of interleukin (IL) 6, IL-10, and IL-13 were also measured. We detected CD40 only on monocytes from patients with sepsis (mean 6.5 ± 0.4 median channel fluorescence). There was an inverse correlation between peak CD40 expression and survival (P = 0.05), particularly in the patients with bacteremia (P = 0.019). In the bacteremic group, there was an inverse correlation between CD40 expression and bilirubin levels (r2 = 0.52, P = 0.004) and plasma IL-6 concentrations (r2 = 0.30, P = 0.04). Our results showed that upregulation of CD40 expression on peripheral blood monocytes is a protective phenomenon during severe sepsis. Monocyte deactivation reflected by low CD40 expression may represent impairment of immune function associated with severity of illness and poor outcome. Further studies on monocyte phenotype and function may help to assess the immune status of patients with sepsis and perhaps be useful to guide immunomodulatory strategy in the future.

Severe atherosclerosis of the aorta and development of peripheral T-cell lymphoma in an adolescent with angiolymphoid hyperplasia with eosinophilia

We report an adolescent girl with a history of angiolymphoid hyperplasia with eosinophilia (ALHE) diagnosed at the age of 10 years. The patient also suffered from chronic persistent multiresistant herpes simplex virus infection. Atherosclerotic occlusive disease of the abdominal aorta and its major branches was observed at the age of 17 years, necessitating vascular surgical intervention 1 year later because of disease progression. Histological examination of the aorta disclosed widespread atherosclerosis and high levels of gene expression of both T‐helper cell type (Th) 1‐ and Th2‐derived cytokines. This suggests that a highly stimulated systemic immune response including increased production of both Th1‐ and Th2‐derived cytokines such as interferon‐γ and interleukin‐4 may result in severe atherosclerotic lesions at a very young age. In addition, the patient developed a peripheral T‐cell lymphoma at the age of 18 years. Neither systemic atherosclerosis nor T‐cell lymphoma has been reported in association with ALHE. It is suggested that a highly stimulated dysfunctional immune response may play a key role in persistent inflammatory disease and premature development of atherosclerosis as well as malignant transformation of T cells.

CD8+ T-Cell Subpopulations in Human Abdominal Aortic Aneurysm Lesion

To the Editor: We read with interest the article by Duftner et al1 reporting the prevalence of peripheral interferon-γ (IFN-γ)–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 IFN-γ prevents the induction of experimental AAA in a calcium chloride–induced mouse model,4 AAA formation being reconstituted by administration of IFN-γ into CD4−/− mice or infusion of competent splenocytes from wild-type mice into IFN-γ−/− 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 IFN-γ and 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 …

Patient prognosis with critical limb ischemia: an update of 164 patients

It is generally considered that patients with rest pain and/or ulceration have a bad prognosis independent of the type of treatment given. Many factors can reasonably explain this evolution; the main ones are: multifocal atherosclerotic disease in most instances with a high death frequency secondary to myocardial infarction and stroke, morbidity and mortality secondary to amputations, and higher risk of both arterial and venous thromboembolic disease.