title: A septin requirement differentiates autonomous and contact-facilitated T cell proliferation.
abstract: 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.
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Mujal
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Gilden
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Gérard
authors.affiliation: Division of Biological Sciences, Nagoya University Graduate School of Science, Nagoya, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Krummel
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D020013:Calcium Signaling; D049109:Cell Proliferation / Q000235:genetics*; D016207:Cytokines / Q000494:pharmacology; D048749:Cytokinesis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D015151:Immunoblotting; D016023:Integrins; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell; D050799:STAT5 Transcription Factor / Q000378:metabolism; D058112:Septins / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D016023:Integrins; D011948:Receptors, Antigen, T-Cell; D050799:STAT5 Transcription Factor; D019869:Phosphatidylinositol 3-Kinases; C512895:Sept7 protein, mouse; D058112:Septins