title: Murine NK cell intrinsic cytokine-induced memory-like responses are maintained following homeostatic proliferation.
abstract: Several recent studies have demonstrated that innate immune NK cells exhibit memory-like properties with enhanced nonspecific and specific recall responses. Cytokine activation alone of murine NK cells induces the differentiation of memory-like cells that are more likely to produce IFN-γ, a key NK cell cytokine important for activation of the immune response. Using an adoptive cotransfer system, we first show that cytokine-induced memory-like responses are NK intrinsic. However, engraftment of donor NK cells in NK-competent hosts is poor because of homeostatic control mechanisms. Therefore, we used alymphoid Rag- and common γ-chain-deficient mice as recipients and observed homeostatic expansion of cotransferred cytokine-activated and control donor NK cells. Despite proliferation of all cells, NK cells derived from those cells originally activated by cytokines retained an intrinsic enhanced capacity to produce IFN-γ when restimulated in vitro with cytokines or target cells. These NK cell memory-like responses persisted for at least 4 wk in alymphoid hosts and 12 wk in NK-competent hosts. These findings indicate that memory-like NK cells can readily self-renew and maintain enhanced function in a lymphopenic host for at least a month.
authors.affiliation: Division of Rheumatology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Molly P
authors.initials: MP
authors.lastname: Keppel
authors.forename: Liping
authors.initials: L
authors.lastname: Yang
authors.forename: Megan A
authors.initials: MA
authors.lastname: Cooper
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
chemical_list: D016207:Cytokines; D011948:Receptors, Antigen, T-Cell