A septin requirement differentiates autonomous and contact-facilitated T cell proliferation

作者：Mujal Adriana M; Gilden Julia K; Gerard Audrey; Kinoshita Makoto; Krummel Matthew F^*

来源：Nature Immunology, 2016, 17(3): 315-322.

DOI：10.1038/ni.3330

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 cytokinedriven proliferation without influencing expansion driven by conventional antigen-presentation.

• 出版日期2016-3