Journal
JOURNAL OF IMMUNOLOGY
Volume 180, Issue 7, Pages 4679-4686Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.180.7.4679
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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 lympboid 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-15R alpha, 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-15R alpha and CCR5 in autoimmune disorders in which NK cells play a deleterious role.
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