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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.

Original publication

DOI

10.1371/journal.pone.0026138

Type

Journal article

Journal

PloS one

Publication Date

01/2011

Volume

6

Addresses

Department of Pathology, University of California San Francisco, San Francisco, California, United States of America.

Keywords

Dendritic Cells, Follicular, Lymph Nodes, T-Lymphocytes, Th1 Cells, Cell Line, Stromal Cells, Animals, Mice, Signal Transduction, Cell Cycle, Transcription, Genetic, Up-Regulation, Nitric Oxide Synthase Type II, Interferon-gamma, Feedback, Physiological