Regulatory T cells control dendritic cell/NK cell cross-talk in lymph nodes at the steady state by inhibiting CD4+ self-reactive T cells.
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.
Terme
Magali
M
Institut National de la Santé et de la Recherche Médicale Unité 805, Tumor Immunology and Immunotherapy, Villejuif, France
Chaput
Nathalie
N
Combadiere
Behazine
B
Ma
Averil
A
Ohteki
Toshiaki
T
Zitvogel
Laurence
L
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D053720:Interleukin-15 Receptor alpha Subunit / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019713:Receptors, CCR5 / Q000276:immunology
D053720:Interleukin-15 Receptor alpha Subunit; D019713:Receptors, CCR5