T cell activation through the Ag receptor (TCR) requires sustained signaling from signalosomes within lipid raft microdomains in the plasma membrane. In a proteomic analysis of lipid rafts from human T cells, we identified stomatin-like protein (SLP)-2 as a candidate molecule involved in T cell activation through the Ag receptor. In this study, we show that SLP-2 expression in human primary lymphocytes is up-regulated following in vivo and ex vivo activation. In activated T cells, SLP-2 interacts with components of TCR signalosomes and with polymerized actin. More importantly, up-regulation of SLP-2 expression in human T cell lines and primary peripheral blood T cells increases effector responses, whereas down-regulation of SLP-2 expression correlates with loss of sustained TCR signaling and decreased T cell activation. Our data suggest that SLP-2 is an important player in T cell activation by ensuring sustained TCR signaling, which is required for full effector T cell differentiation, and point to SLP-2 as a potential target for immunomodulation.
Pretransplant EBV-seronegative status is a strong risk for development of PTLD in adult renal allograft recipients, even in late disease. These results indicate that primary infection with EBV may have a pathogenic role in some cases of late PTLD.
Rosai–Dorfman disease is a rare lymphoproliferative disorder that can have nodal and extranodal manifestations. In the absence of established guidelines for the management of this condition, various therapeutic modalities are used, including radiotherapy. Radiation dosages and fractionation schedules have not been reported in all instances. We present a case in which glottic and subglottic Rosai–Dorfman lesions causing airway obstruction in a frail steroid-refractory patient were put into complete remission using radiotherapy. The lesions responded transiently to a course of prednisone, but responded completely to external-beam radiation, with minimal side effects to the patient.
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