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T cell proliferation is initiated by T cell antigen receptor (TCR) triggering, soluble growth factors or both. In characterizing T cells lacking the septin cytoskeleton, we found that successful cell division has discrete septin-dependent and septin-independent pathways. Septin-deficient T cells failed to complete cytokinesis when prompted by pharmacological activation or cytokines. In contrast, cell division was not dependent on septins when cell-cell contacts, such as those with antigen-presenting cells, provided a niche. This septin-independent pathway was mediated by phosphatidylinositol-3-OH kinase activation through a combination of integrins and costimulatory signals. We were able to differentiate between cytokine- and antigen-driven expansion in vivo and thus show that targeting septins has strong potential to moderate detrimental bystander or homeostatic cytokine-driven proliferation without influencing expansion driven by conventional antigen-presentation.

Original publication

DOI

10.1038/ni.3330

Type

Journal article

Journal

Nat Immunol

Publication Date

03/2016

Volume

17

Pages

315 - 322

Keywords

Animals, Antigen-Presenting Cells, CD8-Positive T-Lymphocytes, Calcium Signaling, Cell Proliferation, Cytokines, Cytokinesis, Flow Cytometry, Immunoblotting, Integrins, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Microscopy, Confocal, Phosphatidylinositol 3-Kinases, Phosphorylation, Receptors, Antigen, T-Cell, STAT5 Transcription Factor, Septins