Rapid death and regeneration of NKT cells in anti-CD3epsilon- or IL-12-treated mice: a major role for bone marrow in NKT cell homeostasis.
Natural killer T (NKT) cells express a T cell receptor (TCR) and markers common to NK cells, including NK1.1. In vivo, NKT cells are triggered by anti-CD3epsilon MAb to rapidly produce large amounts of IL-4 and by IL-12 to reject tumors. We show here that anti-CD3epsilon MAb treatment rapidly depletes the liver (and partially the spleen) of NKT cells and that homeostasis is achieved 1 to 2 days later via NKT cell proliferation that occurs mainly in bone marrow. Similar results were obtained in mice treated with IL-12. Collectively, our data demonstrate that peripheral NKT cells are highly sensitive to activation-induced cell death and that bone marrow plays a major role in restoring NKT cell homeostasis.
Ludwig Institute for Cancer Research Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
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Eberl
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MacDonald
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D000941:Antigens / Q000032:analysis; D000950:Antigens, Ly; D000954:Antigens, Surface; D017209:Apoptosis; D001853:Bone Marrow / Q000502:physiology; D017252:CD3 Complex / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006706:Homeostasis; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology*; D037181:Lectins, C-Type; D008099:Liver / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000032:analysis; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology
D000911:Antibodies, Monoclonal; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D017252:CD3 Complex; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D018664:Interleukin-12