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

Gérard A., Khan O., Beemiller P., Oswald E., Hu J., Matloubian M., Krummel MF.

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.

DOI

10.1038/ni.2547

Type

Journal article

Journal

Nat immunol

Publication Date

04/2013

Volume

14

Pages

356 - 363

Keywords

Animals, Antigen-Presenting Cells, CD8-Positive T-Lymphocytes, Cell Communication, Cell Differentiation, Cytokines, Immunologic Memory, Immunological Synapses, Mice, Mice, Knockout, T-Lymphocyte Subsets

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