A key role in the communication between the ␣TCR and the CD3/ complex is played by a specific motif within the connecting peptide domain of the TCR ␣ chain (␣-CPM). T cell hybridomas expressing an ␣-CPM-mutated TCR show a dramatic impairment in antigen-driven interleukin-2 production. This defect can be complemented by a calcium ionophore, indicating that activation of the calcium pathway is impaired. Several lines of evidence implicate Fyn in the regulation of calcium mobilization, at least in part through the activation of phospholipase C␥. Here we have investigated the potential involvement of Fyn in the TCR ␣-CPM signaling defect. Using T cell hybridomas expressing either a wild-type TCR or an ␣-CPM mutant, we show that Fyn fails to be activated by the mutant receptor following SEB binding and fails to generate tyrosine-phosphorylated Pyk2, a member of the focal adhesion kinase family. This defect correlated with an impairment in phospholipase C␥ phosphorylation. Production of interlukin-2 and activation of the transcription factor NF-AT in response to triggering of the TCR ␣-CPM mutant with SEB were fully restored in the presence of constitutively active Fyn. Hence the signaling defect generated by the TCR ␣-CPM mutation results at least in part from an impaired coupling of the TCR⅐CD3 complex to Fyn activation.
The 25-gauge 7,500 cpm vitrectomy is an effective and safe surgical procedure, and it can significantly reduce core vitrectomy time in eyes undergoing vitreoretinal surgery.
Dysfunction of the retinal pigmented epithelium (RPE) is one of the first effects of dry age-related macular degeneration (AMD) with consequent blindness. Hence, patients affected by this retinal disorder could benefit from a cell-based transplantation strategy for RPE. Actually, an effective protocol to approach this problem is lacking, though recently, it has been postulated the existence of a subpopulation of RPE stem cells (RPESCs) derived from adult RPE and able to reconstitute a functional RPE. On the other hand, the evidence related to the differentiative potential of human mesenchymal stem cells (MSCs) is continuously increasing. Among others, amniotic fluid-derived MSCs (AF-MSCs) may be a promising candidate, since these cells are characterized by high proliferation and differentiative potential. In this study, AF-MSCs and RPESCs were isolated, characterized to assay their stemness and induced to neuronal/retinal differentiation; specific RPE markers were then analyzed. Our results indicate that RPESCs are more suitable candidates for RPE replacement than AF-MSCs.
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