Murine NK cell intrinsic cytokine-induced memory-like responses are maintained following homeostatic proliferation

MP Keppel, L Yang, MA Cooper - The Journal of Immunology, 2013 - journals.aai.org
MP Keppel, L Yang, MA Cooper
The Journal of Immunology, 2013journals.aai.org
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 …
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.
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