Homeostatic proliferation generates long-lived natural killer cells that respond against viral infection.
Cells of the immune system undergo homeostatic proliferation during times of lymphopenia induced by certain viral infections or caused by chemotherapy and radiation treatment. Natural killer (NK) cells are no exception and can rapidly expand in number when placed into an environment devoid of these cells. We explored the lifespan and function of mouse NK cells that have undergone homeostatic proliferation in various settings of immunodeficiency. Adoptive transfer of mature NK cells into lymphopenic mice resulted in the generation of a long-lived population of NK cells. These homeostasis-driven NK cells reside in both lymphoid and nonlymphoid organs for >6 mo and, similar to memory T cells, self-renew and slowly turn over at steady state. Furthermore, homeostatically expanded NK cells retained their functionality many months after initial transfer and responded robustly to viral infection. These findings highlight the ability of mature NK cells to self-renew and possibly persist in the host for months or years and might be of clinical importance during NK cell adoptive immunotherapy for the treatment of certain cancers.
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Joseph C
JC
Sun
Joshua N
JN
Beilke
Natalie A
NA
Bezman
Lewis L
LL
Lanier
D019264:Adoptive Transfer; D000818:Animals; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology*; D008231:Lymphopenia / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors
D004268:DNA-Binding Proteins; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; C499308:Rag2 protein, mouse
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