Adaptive immune features of natural killer cells

Abstract

In an adaptive immune response, naïve T cells proliferate during infection and generate long-lived memory cells that undergo secondary expansion following re-encounter with the same pathogen. Although Natural Killer cells traditionally have been classified as cells of the innate immune system, they share many similarities with cytotoxic T lymphocytes. In a mouse model of cytomegalovirus (MCMV) infection, we demonstrate that, like T cells, NK cells bearing the virus-specific Ly49H receptor proliferate 100-fold in the spleen and 1000-fold in the liver following infection. Following a contraction phase, Ly49H+ NK cells reside in lymphoid and non-lymphoid organs for several months. These self-renewing “memory” NK cells rapidly degranulate and produce cytokines upon reactivation. Adoptive transfer of these NK cells into naïve animals followed by viral challenge results in a robust secondary expansion and protective immunity. These findings reveal novel properties of NK cells previously attributed only to cells of the adaptive immune system.

Natural killer cell memory in infection, inflammation and cancer

“…Sun et al demonstrated that NK cell memory responses against mouse cytomegalovirus (MCMV) exist and that memory NK cells can reside in organs other than the liver, with these cells being identified in the spleen, blood circulation, lung, kidney and other lymphoid tissues 16,17 . Paust et al 14 reported that after subcutaneous immunization of mice with noninfectious virus-like particles (VLPs) containing proteins from influenza virus or HIV-1 or with ultra violet light-inactivated vesicular stomatitis virus (VSV), the transfer of hepatic NK cells resulted in prolonged survival of the mice after a lethal challenge with the sensitizing virus, but not with an unrelated virus.…”

“…However, in 2007, it was reported that the MCMVencoded MHC class I-like glycoprotein m157 engages LY49H to activate NK cells and confers host protection in MCMV-resistant C57BL/6 mice 28,29 . The existence of a MCMV-specific receptor, LY49H, and a specific viral antigen, m157, facilitated subsequent studies tra cing the expansion, contraction and differentiation of MCMVspecific NK cells into a long-lived, self-renewing memory subset 16 . In the absence of LY49H or m157, this activation programme is not induced, indicating a non-redundant role of the LY49H-m157 axis in this process.…”

“…In the MCMV infection model, LY49H + memory NK cells produce higher amounts of IFNγ as compared with naive NK cells, demonstrate more robust cytotoxic responses and provide enhanced host protection following reinfection with MCMV, but not following infection with heterologous pathogens 16,68 . In human studies, Romagnani and colleagues demonstrated that the CD94-NKG2C + NK cell populations that expanded in HCMV-seropositive individuals exhibited a demethy lated CNS1 region in the IFNG locus 62 .…”

Homéostasie des cellulesnatural killer

“…L'interaction entre m157 et Ly49H entraîne une prolifération intense des cellules NK Ly49H + qui représentent environ 50 % des cellules NK à l'état basal [29]. Lorsqu'un petit nombre de cellules NK Ly49H + est transféré à des souris Ly49H -qui sont ensuite infectées par MCMV, l'expansion des cellules NK Ly49H + est comparable à l'expansion clonale des précur-seurs T naïfs qui a lieu lors de leur rencontre avec l'antigène spécifique [30]. Ce résultat a ainsi démontré que les cellules NK partagent dans SYNTHÈSE REVUES ces cellules chez des individus normaux restent encore à démontrer [38], il n'en demeure pas moins que le phénomène de « mémoire NK » pourrait être utilisé dans des contextes cliniques en exploitant d'une part, l'amé-lioration des fonctions des cellules NK « mémoires » et, d'autre part, leur capacité à persister à moyen terme et peut-être même à long terme chez des individus lymphopéniques (suite à une chimiothérapie par exemple).…”

Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity

“…Humans lacking NK cells are susceptible to severe infections with human herpes viruses, including CMV (Biron et al 1989;Orange 2002). Intriguingly, recent evidence in mice suggest that NK cell responses to an array of chemical and viral antigens also involve adaptive immune features such as expansion and contraction of subpopulations of NK cells with specific and heightened responses to subsequent rechallenges with the same antigen (O' Leary et al 2006;Paust et al 2010;Sun et al 2009). In humans, such adaptive behavior has been observed in the context of both acute and latent CMV infection (Foley et al 2012;Guma et al 2006b;LopezVerges et al 2011).…”