Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes

Veronika Lukacs-Kornek, Deepali Malhotra, Anne L Fletcher, Sophie E Acton, Kutlu G Elpek, Prakriti Tayalia, Ai-Ris Y Collier, Shannon J Turley

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182 Citations (Scopus)

Abstract

Fibroblastic reticular cells (FRCs) and lymphatic endothelial cells (LECs) are nonhematopoietic stromal cells of lymphoid organs. They influence the migration and homeostasis of naive T cells; however, their influence on activated T cells remains undescribed. Here we report that FRCs and LECs inhibited T cell proliferation through a tightly regulated mechanism dependent on nitric oxide synthase 2 (NOS2). Expression of NOS2 and production of nitric oxide paralleled the activation of T cells and required a tripartite synergism of interferon-gamma, tumor necrosis factor and direct contact with activated T cells. Notably, in vivo expression of NOS2 by FRCs and LECs regulated the size of the activated T cell pool. Our study elucidates an as-yet-unrecognized role for the lymph node stromal niche in controlling T cell responses.
Original languageEnglish
Pages (from-to)1096 - 1104
Number of pages9
JournalNature Immunology
Volume12
Issue number11
DOIs
Publication statusPublished - 2011
Externally publishedYes

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