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Nat Immunol. 2013 Apr;14(4):356-63. doi: 10.1038/ni.2547. Epub 2013 Mar 10.

Secondary T cell-T cell synaptic interactions drive the differentiation of protective CD8+ T cells.

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Department of Pathology, University of California, San Francisco, San Francisco, California, USA.


Immunization results in the differentiation of CD8+ T cells, such that they acquire effector abilities and convert into a memory pool. Priming of T cells takes place via an immunological synapse formed with an antigen-presenting cell (APC). By disrupting synaptic stability at different times, we found that the differentiation of CD8+ T cells required cell interactions beyond those made with APCs. We identified a critical differentiation period that required interactions between primed T cells. We found that T cell-T cell synapses had a major role in the generation of protective CD8+ T cell memory. T cell-T cell synapses allowed T cells to polarize critical secretion of interferon-γ (IFN-γ) toward each other. Collective activation and homotypic clustering drove cytokine sharing and acted as regulatory stimuli for T cell differentiation.

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