title: IL-2-dependent adaptive control of NK cell homeostasis.
abstract: Activation and expansion of T and B lymphocytes and myeloid cells are controlled by Foxp3(+) regulatory T cells (T reg cells), and their deficiency results in a fatal lympho- and myeloproliferative syndrome. A role for T reg cells in the homeostasis of innate lymphocyte lineages remained unknown. Here, we report that T reg cells restrained the expansion of immature CD127(+) NK cells, which had the unique ability to up-regulate the IL2Rα (CD25) in response to the proinflammatory cytokine IL-12. In addition, we observed the preferential accumulation of CD127(+) NK cells in mice bearing progressing tumors or suffering from chronic viral infection. CD127(+) NK cells expanded in an IL-2-dependent manner upon T reg cell depletion and were able to give rise to mature NK cells, indicating that the latter can develop through a CD25(+) intermediate stage. Thus, T reg cells restrain the IL-2-dependent CD4(+) T cell help for CD127(+) immature NK cells. These findings highlight the adaptive control of innate lymphocyte homeostasis.
authors: Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors: Georg
authors: G
authors: Gasteiger
authors: Saskia
authors: S
authors: Hemmers
authors: Paula D
authors: PD
authors: Bos
authors: Joseph C
authors: JC
authors: Sun
authors: Alexander Y
authors: AY
authors: Rudensky
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D018664:Interleukin-12
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