Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection

Abstract

Nabekura and Lanier demonstrate that two distinct long-lived NK cell subsets with different functional properties differentiate during mouse model of cytomegalovirus (MCMV) infection. NK cells expressing the MCMV-specific Ly49H receptor differentiated into memory NK cells and Ly49H− NK cells differentiated into cytokine-activated NK cells. Memory NK cells show enhanced effector function, whereas cytokine-activated NK cells persisted better in an MCMV-free environment.

The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

“…However, several observations suggest the possibility that different NK cell subsets act against distinct pathogens or in a different manner. This is attested by the recent evidence that mouse Ly49H + and Ly49H − NK cell subsets give a complementary protection to MCMV differentiating into memory-like and cytokine-activated NK cells, respectively [105]. A similar behavior has been reported both for mouse liver CD49a + /DX5 − and CD49a − /DX5 + and for human peripheral blood CD56 dim /CD16 bright and CD56 bright /CD16 dim/neg NK cell subsets.…”

Memory responses of natural killer cells

“…A recent study addressed this question using an inducible reporter system to track endogenous NK cell populations following MCMV infection in mice [109]. The authors demonstrated that both Ly49H + and Ly49H − NK cells are long-lived following infection, indicating that NK cells lacking Ly49H can differentiate into cytokine-activated memory-like cells following MCMV infection, and that a single infection can drive multiple subsets of memory NK cells [109].…”

“…A recent study addressed this question using an inducible reporter system to track endogenous NK cell populations following MCMV infection in mice [109]. The authors demonstrated that both Ly49H + and Ly49H − NK cells are long-lived following infection, indicating that NK cells lacking Ly49H can differentiate into cytokine-activated memory-like cells following MCMV infection, and that a single infection can drive multiple subsets of memory NK cells [109]. Whereas the Ly49H + memory NK cells displayed enhanced effector function and anti-tumor activity in vivo , the Ly49H − memory NK cells expressed higher levels of Bcl2 and persisted better following transfer into naïve hosts [109].…”

“…The authors demonstrated that both Ly49H + and Ly49H − NK cells are long-lived following infection, indicating that NK cells lacking Ly49H can differentiate into cytokine-activated memory-like cells following MCMV infection, and that a single infection can drive multiple subsets of memory NK cells [109]. Whereas the Ly49H + memory NK cells displayed enhanced effector function and anti-tumor activity in vivo , the Ly49H − memory NK cells expressed higher levels of Bcl2 and persisted better following transfer into naïve hosts [109]. Notably, the Ly49H − memory NK cells exhibited some functional differences as compared with in vitro cytokine-induced memory cells, suggesting that an in vivo infection-induced cytokine milieu may imprint unique features on the resulting memory cells.…”

Cutting Edge: NKG2D Signaling Enhances NK Cell Responses but Alone Is Insufficient To Drive Expansion during Mouse Cytomegalovirus Infection

“…NK cells have adaptive immune features, which include antigen-specific proliferation after exposure to mouse cytomegalovirus (MCMV) and alloantigens (3–6). We have previously demonstrated that mouse NK cells expressing Ly49H, which specifically recognizes the m157 MCMV glycoprotein on infected cells (7), robustly expand after MCMV infection (4).…”