title: Regulation of T cell priming by lymphoid stroma.
abstract: The priming of immune T cells by their interaction with dendritic cells (DCs) in lymph nodes (LN), one of the early events in productive adaptive immune responses, occurs on a scaffold of lymphoid stromal cells, which have largely been seen as support cells or sources of chemokines and homeostatic growth factors. Here we show that murine fibroblastic reticular cells (FRCs), isolated from LN of B6 mice, play a more direct role in the immune response by sensing and modulating T cell activation through their upregulation of inducible nitric oxide synthase (iNOS) in response to early T cell IFNγ production. Stromal iNOS, which only functions in very close proximity, attenuates responses to inflammatory DC immunization but not to other priming regimens and preferentially affects Th1 cells rather than Th2. The resultant nitric oxide production does not affect T cell-DC coupling or initial calcium signaling, but restricts homotypic T cell clustering, cell cycle progression, and proliferation. Stromal feedback inhibition thus provides basal attenuation of T cell responses, particularly those characterized by strong local inflammatory cues.
authors: Department of Pathology, University of California San Francisco, San Francisco, California, United States of America.
authors: Omar
authors: O
authors: Khan
authors: Mark
authors: M
authors: Headley
authors: Audrey
authors: A
authors: Gerard
authors: Wei
authors: W
authors: Wei
authors: Limin
authors: L
authors: Liu
authors: Matthew F
authors: MF
authors: Krummel
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000276:immunology; D002460:Cell Line; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D025461:Feedback, Physiological; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D017154:Stromal Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II