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Background: Infection with microorganisms is considered a pathogenic factor in atherogenesis. Several studies have shown the presence of a broad spectrum of bacterial species in atherosclerotic plaques, which could trigger local inflammation. Because T cells contribute to atherosclerotic plaque inflammation, we studied the responsiveness of human plaque derived T-cell cultures to bacteria of different species., Materials and Methods: Primary polyclonal T-cell cultures were generated from both carotid endarterectomy tissue and peripheral blood of nine patients, and the peripheral blood of eight matched controls. The in vitro proliferative responses of the T-cell cultures against H. pylori, N. meningitidis, N. lactamica, S. aureus, S. pneumoniae, S. epidermidis and E. coli were analysed. T-cell proliferation was measured by (3)H-thymidine incorporation and expressed as a stimulation index. Selective outgrowth of intraplaque microbial specific T cells was studied by calculating the ratio of plaque T-cell SI and peripheral blood T-cell SI in each patient., Results: All patients showed T-cell responsiveness to multiple bacteria in their plaque tissue. Stimulation indices were in the range of 0.3-30, and this degree of reactivity with the different species was heterogeneous among patients. Selective outgrowth (plaque/peripheral blood ratio) of T cells against multiple bacteria was observed in six out of nine patients., Conclusions: T cells in atherosclerotic plaques have the capacity to selectively respond to antigens of a wide variety of microbial antigens. This supports the view that such mechanisms could contribute to the atherosclerotic inflammatory response.

T-cell activation in atherosclerotic plaques is thought to be initiated by plaque-derived antigens, such as oxidized LDL (oxLDL). An alternative pathway of T-cell activation independent of antigen stimulation, mediated by the cytokine interleukin (IL)-15, was recently described. We investigated IL-15 expression in atherosclerotic plaques in relation to plaque morphology, inflammatory cells, T-cell activation, and oxidation-specific epitopes by use of immunohistochemistry. In situ hybridization was used to evaluate IL-15 mRNA expression. We also studied the proliferative response of plaque-derived T-cell lines to IL-15 in vitro using [(3)H]thymidine incorporation. Fresh-frozen specimens were classified as fibrous (n=9), fibrolipid (n=8), and lipid-rich (n=14) plaques; normal vessels (n=4) served as reference. Expression of IL-15 mRNA and protein was found almost solely in fibrolipid and lipid-rich plaques, associated with oxLDL-positive macrophages. Sequential immunostains revealed colocalization between IL-15- and CD40L-positive T cells. Moreover, plaque-derived T-cell lines were highly responsive to IL-15. Hence, IL-15 could provide a pathway for antigen-independent T-cell activation.

T cells take part in the chronic inflammatory reaction in atherosclerotic plaques, but their specific role in atherosclerosis has not yet been fully elucidated. Nevertheless, one may anticipate that activated T cells may secrete cytokines capable of modulating the morphology and hence the stability of plaques by regulating cell proliferation, lipid metabolism, and extracellular matrix (ECM) synthesis and/or degradation. This study has been designed to investigate the functional properties of T cells in atherosclerotic lesions. For this purpose, T-cell clones were generated from atherosclerotic plaques isolated from human aortas obtained at autopsy from six subjects. Cloned cells were activated with PMA and OKT-3 to initiate cytokine production and cytokine profiles of CD4-positive clones were measured by ELISA. The majority of the T-cell clones (125/155, 81 per cent) produced both interferon (IFN)-gamma and interleukin (IL)-4 (type 0 cytokine profile). Moreover, the production of IFN-gamma was dominant in the majority of these clones. A type 1 cytokine profile (high levels of IFN-gamma and low levels of IL-4) was found in 17 per cent of the clones (27/155). Only three clones (2 per cent) showed a type 2 cytokine secretion pattern (high levels of IL-4 and low levels of IFN-gamma). No cytolytic activity could be established in plaque-derived T cells. Our results show that the T-cell population in atherosclerotic lesions is heterogeneous, but the most dominant T cell by far is the one with a type 0 cytokine profile. The dominant secretion of IFN-gamma by T-cell clones suggest an important role for plaque T cells in modulating the growth and differentiation of other cells, such as macrophages and smooth muscle cells in atherosclerotic plaques., (Copyright 1999 John Wiley & Sons, Ltd.)

Objective: To discriminate between chronic inflammation and acute activation of the plaque immune response in culprit lesions of patients with acute coronary syndromes., Design: Retrospective study., Setting: Tertiary referral centre., Subjects: 71 patients having coronary atherectomy were classified according to their ischaemic syndrome: stable angina (n = 23); stabilised unstable angina (n = 18); refractory unstable angina (n = 11); and acute myocardial infarction (n = 19)., Main Outcome Measures: Immunohistochemical measurement of interleukin 2 receptor (IL-2R) (CD25) positive cells expressed as a percentage of the total amount of (CD3 positive) T lymphocytes in frozen sections of atherectomy specimens., Results: The number of lesions containing IL-2R (CD25) positive T cells increased with severity of the ischaemic coronary syndrome (stable angina, 52%; stabilised unstable angina, 77.8%; refractory unstable angina, 90.9%; acute myocardial infarction, 89.4%). The percentage of activated T cells (CD25/CD3 ratios x100) increased in lesions associated with refractory unstable angina (7.8%) and acute myocardial infarction (18.5%), compared with those in lesions associated with either chronic stable angina (2.2%) or stabilised unstable angina (3.3%)., Conclusions: An increase in the percentage of IL-2R positive T lymphocytes in culprit lesions of patients with acute coronary syndromes indicates recent activation and amplification of the immune response within plaques. This may result in a burst of inflammatory products with tissue degrading and vasoactive properties and, hence, could initiate or accelerate the onset of an acute coronary event.

T-cell activation probably plays the most important role in hyperproliferation of keratinocytes in psoriasis. We present here our results concerning the interacting immunocompetent cells and their phenotypic and functional characteristics in relation to psoriasis pathology. Immunohistochemical analysis of skin biopsies from psoriasis patients, did indeed show that hyperproliferation of keratinocytes is associated with increased vasculature and increased influx of MHC class II molecules expressing immunocompetent cells. Furthermore, in psoriasis, several adhesion molecules and other relevant activation markers were found to be upregulated even in the non-lesional psoriatic skin, indicating that psoriatic skin in general is in an activated state. This interpretation is further supported by the observation that the expression of several AR and other relevant activation markers when compared with those in non-lesional skin from contact dermatitis are increased in a significant manner in the non-lesional skin of psoriasis patients. We have then followed up our investigations by generating T-cell lines from lesional psoriatic skin and studied their adhesion patterns on cultured endothelial cells in order to get better insight into the migration pattern of different T cell subsets in psoriasis pathology. Our results indicate that different T-cell subsets CD4+, CD8+ (both TCR-alpha beta+) CD4-/CD8+ TCR-gamma delta+ and CD4-CD8-TCR-gamma delta (V delta 1-) T-cells can easily be generated from psoriatic patients. In a comparative kinetic study using unstimulated and stimulated cultured human umbilical vein endothelial cells, we observed that TCR-gamma delta T cells showed different adhesion properties from that of TCR-alpha beta+ T cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

The immigration of circulating T cells into specific tissues is directed by the interaction between adhesion molecules on lymphocyte subpopulations and their ligands on vascular endothelium. Of these, endothelial leucocyte adhesion molecule (ELAM-1), weakly expressed in normal human skin (NHS), seems to be the counter-structure for cutaneous lymphocyte-associated antigen (CLA). CLA is a 200 kDa cell-surface glycoprotein of which the sugar moieties sialyl Le(a) and sialyl Le(x) are the possible epitopes recognized by the monoclonal antibody HECA-452. HECA-452 was originally described as a marker for lymphoid organ high endothelial cells, but 16% of peripheral-blood-derived T cells react with this antibody. We studied the expression of CLA on the cellular constituents of the skin immune system (SIS). By applying immunohistochemical double staining, 41% of CD3+ T cells, 44% of CD4+ T cells and 31% of CD8+ T cells were found to express CLA. Keratinocytes, CD1a+ Langerhans cells (LC) and endothelial cells did not express HECA-452 in significant numbers in NHS. Monocytes were found to express HECA-452 in 14% of CD68+ cells. CLA expression was present on a relatively low percentage of T cells and subsets localized distant from NHS vessels, suggesting loss of the molecule during further migration after transendothelial passage. However, intraepidermal T cells expressed CLA in similar percentages to T cells localized directly perivascularly. Our findings support the notion that CLA expression by T cells is associated with their homing into cutaneous structures.