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Introduction: Increasing evidence suggest that an interplay between T cells and fibroblasts plays a pivotal role in promoting matrix accumulation in systemic sclerosis (SSc). Aim: We investigated if the co-culturing of fibroblasts derived from SSc patients with autologous PBMCs could induce peculiar modifications in any cell types. Materials and methods: Fibroblasts were obtained from the skin of patients undergoing biopsy for diagnostic purposes. PBMCs were obtained from the same patients. All the patients were fully informed of the meaning of the study and accepted to donate blood. Cells were taken in culture at 37 ˚C5% CO2 for ten days, then cells were stained with monoclonal antibodies for HLA-DR, CD3, CD4, CD56, CD95, TCRab, TCRcd, After the staining, cells were analyzed by flow-cytometry using a FACScalibur. Results: We found that T cells bearing an ab receptor were expanded in the co-cultures. Moreover, these cells were positive for the expression of HLA-DR, suggesting an activation of T cells induced by co-culturing with autologous fibroblasts. No expansion of cd T cells nor CD56 positive T cells was found. SSc fibroblasts, which have already been reported to have a basal high expression of CD95 (FAS), were found to up-regulate FAS in these experiments. Conclusions: We recently showed that peripheral blood T cells from SSc patients expand when co-cultured with autologous fibroblasts and acquire the same T cell clonotypes that are increased in the affected skin. The results presented here further support that such expansion may be due to a specific antigenic activity of fibroblasts on T cells. In addition, the up-regulation of FAS expression on SSc fibroblasts may be related to phenotypic changes that indicate an increased ability of these cells to escape normal pathways leading to cell death. The meaning of these findings in the pathogenesis of SSc remains to be further investigated.

During the last two decades, a new perspective on atherosclerosis has prevailed based on accumulating evidence on the role of inflammatory and immune-competent cells, such as monocytes and T-lymphocytes, in contributing to the development of this disease. It is now generally accepted that a specific T-cell response is crucial in determining not only the development and growth of the atherosclerotic lesion, but also its fate toward a stable or an unstable pattern of evolution (i.e., rupture or ulceration), eventually leading to the clinical occurrence of acute coronary syndromes (ACS). We found that transcoronary IL-17 levels tended to be higher in ACS patients as compared to patients with Stable Angina. We observed a bimodal distribution of IL-17 transcoronary gradients, with 10 out of 23 patients showing elevated IL-17 transcoronary gradients. The ACS patients with elevated transcoronary IL-17 levels, showed also a significant increase in the percentage of Th-17 lymphocytes when samples from the coronary sinus were compared to the ones obtained from the Aorta Finally, patients with a Δ% transcoronary IL-17 gradient > 10 showed troponin I (Tn I) levels at admission significantly higher as compared to the levels measured in the patient population with a Δ% transcoronary IL-17 gradient < 10. Intriguingly, a significant correlation between ∆% transcoronary IL-17 levels and Tn I levels at admission was found only in patients with ∆% transcoronary IL-17 levels > 10 while no correlation was found in the other ACS patients. Our findings highlight that expansion of Th-17 lymphocytes, with the consequent increase in transcoronary IL-17 gradient, might have an important pathophysiological role in a subset of patients with ACS. In addition, data about relationship existing between IL-17 and troponin levels, indicate that this subset of patients presents with a more severe disease and suggest that they may possibly have a poorer prognosis.

Background C-reactive protein (CRP) plasma levels correlate with cardiovascular events. Although a direct role for CRP in atherothrombosis has been suggested, at the moment little is known about its involvement in the pathophysiology of acute coronary syndromes (ACS). Thus, the aim of this study was to determine whether CRP is produced in the culprit lesion and released within the coronary circulation of patients with ACS and whether it may affect coronary endothelial function. Methods Blood samples were simultaneously obtained from the aorta (Ao) and the coronary sinus (CS) of patients with normal coronary artery (n=16), stable angina (n=30), and ACS (n=29) for later measurement of plasma CRP levels. Endothelium-dependent and -independent coronary vasodilation were evaluated by means of a Doppler Flow Wire in response to the increasing intracoronary doses of acetylcholine and adenosine, respectively. Results CRP plasma levels were significantly higher across the coronary circulation only in ACS patients with the culprit lesion located in the left coronary artery, while no differences between CS and Ao CRP plasma levels were observed in all other groups. Transcardiac CRP levels were correlated with impairment in coronary endothelium-dependent vasodilation. In six additional patients (SA=3 and ACS=3), subjected to coronary atherectomy, real-time quantitative PCR revealed presence of CRP mRNA only in unstable plaques. Conclusions Thus, CRP is produced and released within the coronary circulation of patients with ACS; this is associated with impairment of endothelial function, suggesting a new pathophysiological link between CRP and ACS.