Regulatory T cells control dendritic cell/NK cell cross-talk in lymph nodes at the steady state by inhibiting CD4+ self-reactive T cells.

Terme M, Chaput N, Combadiere B, Ma A, Ohteki T, Zitvogel L.
J Immunol. 2008 Apr 1;180(7):4679-86.

The CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) play an important role in the control of peripheral tolerance by directly inhibiting conventional T cell proliferative and effector functions. However, the mechanisms by which Treg regulate the homeostasis of lymph nodes remain unclear. In this study, we show in a mouse model that Treg control two major checkpoints dictated by the interaction between self-reactive CD4(+) T cells and resident dendritic cell (DC) in secondary lymphoid organs. First, Treg inhibit the production of CCR5 ligands, limiting the CCR5-dependent recruitment of DC in the lymph nodes. Second, Treg prevent the DC exposure of IL-15Ralpha, markedly interfering in the DC-mediated NK cell proliferation in vivo. Therefore, the DC/T cell autoreactivity leading to NK cell triggering could potentially be controlled by the coinhibition of both IL-15Ralpha and CCR5 in autoimmune disorders in which NK cells play a deleterious role.

URL: http://www.jimmunol.org/cgi/content/full/180/7/4679

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/18354191

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