Previously, only T and B cells were thought able to generate long-lived memory cells; however, recent studies demonstrated that natural killer (NK) cells expressing the activating Ly49H receptor undergo clonal expansion, contraction, and generate long-lived memory cells after infection with mouse cytomegalovirus (MCMV). It is still unclear which subsets of NK cells preferentially give rise to memory NK cells. In this study, we show that expression of killer cell lectin-like receptor G1 (KLRG1) defines short-lived effector cells and precursor for long-lived memory cells. We found that sorted KLRG1-, but not KLRG1+ NK cells can generate memory cells. Interestingly, the percentage of KLRG1+ NK cells is significantly increased in Rag1-/- mice and Rag1-/- NK cells are largely impaired in the generation of memory cells. This phenotype was rescued by mixed bone marrow chimeric (wild-type:Rag1-/-) mice. Notably, the same results were also demonstrated in Tcra-/- or T cell-depleted mice. Meanwhile, the percentage of KLRG1+ NK cells was decreased in germ-free mice and antibiotic treatment enhanced memory generation. We further determined that steady-state cytokines induced by nucleotide-binding, oligomerization domain-containing protein (Nod) 1 and Nod2, but not Myd88 and Trif are responsible for the induction of KLRG1+ NK cells. Taken together, our findings demonstrate that commensal bacteria and T cells reciprocally regulate the generation of long-lived memory NK cells.
- Copyright © 2013 by The American Association of Immunologists, Inc.