Publications by authors named "Gregorio Aversa"

Global collaboration in translational science promises to accelerate the discovery, development and dissemination of new medical interventions. Here, we introduce a new international collaboration of translational science organizations and highlight our initial strategy to reduce or remove bottlenecks in translation.

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To identify novel components of the TCR signaling pathway, a large-scale retroviral-based functional screen was performed using CD69 expression as a marker for T cell activation. In addition to known regulators, two truncated forms of p21-activated kinase 2 (PAK2), PAK2DeltaL(1-224) and PAK2DeltaS(1-113), both lacking the kinase domain, were isolated in the T cell screen. The PAK2 truncation, PAK2DeltaL, blocked Ag receptor-induced NFAT activation and TCR-mediated calcium flux in Jurkat T cells.

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Dendritic cells (DC) are unique in their ability to stimulate naive T cells to proliferate and to differentiate into effector T cells. DC, however, can also inhibit T cell activation and play a role in central and peripheral tolerance. IL-10 has been shown to render DC tolerogenic by unknown mechanisms.

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Background: The activation of T cells, mediated by the T-cell receptor (TCR), activates a battery of specific membrane-associated, cytosolic and nuclear proteins. Identifying the signaling proteins downstream of TCR activation will help us to understand the regulation of immune responses and will contribute to developing therapeutic agents that target immune regulation.

Results: In an effort to identify novel signaling molecules specific for T-cell activation we undertook a large-scale dominant effector genetic screen using retroviral technology.

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IL-10 is a potent inhibitor of T-cell activation and has tolerizing effects on these cells. These effects are primarily mediated via modulation of antigen presenting cell function. Here, it is demonstrated that IL-10 completely inhibits LPS-induced DC maturation, resulting in altered DC-T-cell interactions and reduced T-cell responses.

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