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

V Lukacs-Kornek, D Malhotra, AL Fletcher… - Nature …, 2011 - nature.com
V Lukacs-Kornek, D Malhotra, AL Fletcher, SE Acton, KG Elpek, P Tayalia, A Collier…
Nature immunology, 2011nature.com
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 …
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-γ, 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.
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