Human NK cells: From development to effector functions

Abstract

NK cells are the major lymphocyte subset of the innate immune system that mediates antiviral and anti-tumor responses. It is well established that they develop mechanisms to distinguish self from non-self during the process of NK cell education. Unlike T and B cells, natural killer cells lack clonotypic receptors and are activated after recognizing their target via germline-encoded receptors through natural cytotoxicity, cytokine stimulation, and Ab-dependent cellular cytotoxicity. Subsequently, they utilize cytotoxic granules, death receptor ligands, and cytokines to perform their effector functions. In this review, we provide a general overview of human NK cells, as opposed to murine NK cells, discussing their ontogeny, maturation, receptor diversity, types of responses, and effector functions. Furthermore, we also describe recent advances in human NK cell biology, including tissue-resident NK cell populations, NK cell memory, and novel approaches used to target NK cells in cancer immunotherapy.

Natural Killer Cells as Key Mediators in Type I Diabetes Immunopathology

“…Natural killer cells can be characterized as somewhat a hybrid between the innate or adaptive arms of the immune system. They mature from common lymphoid progenitor cells (CLP), recognize MHC Class I molecules, and exhibit targeted killing of virus-infected or transformed tumorigenic cells without prior sensitization via “missing self”-directed pathways ( 8 , 9 ). They have a large cell body filled with cytolytic granules (perforin, granzyme B) similar to CD8+ effector T cells, but their activity is coordinated by a multitudinous array of both inhibitory and activating receptor-ligand interactions that can alter the NK cell status depending on levels of expression ( 9 ).…”

“…They mature from common lymphoid progenitor cells (CLP), recognize MHC Class I molecules, and exhibit targeted killing of virus-infected or transformed tumorigenic cells without prior sensitization via “missing self”-directed pathways ( 8 , 9 ). They have a large cell body filled with cytolytic granules (perforin, granzyme B) similar to CD8+ effector T cells, but their activity is coordinated by a multitudinous array of both inhibitory and activating receptor-ligand interactions that can alter the NK cell status depending on levels of expression ( 9 ). It is conceivable that the evolution of NKs is a response to viral evasion of the adaptive immunity, thus giving rise to their innate phenotype with adaptive genotypic signature ( 10 ).…”

The Chicken Embryo Model: A Novel and Relevant Model for Immune-Based Studies

“…While NK cell biological functions appear to be highly similar between humans and chickens, it is still unsure how much these cells contribute to the chicken immune response. Indeed, earlier studies showed that the frequency of NK cells in blood, spleen, and cecal tonsils was remarkably low (0.5 to 1% of blood lymphocytes) (98), whereas 5-20% of circulating lymphocytes appear to be NK cells in humans (99). However, other publications still observed an important NK-like activity in chickens (73,100).…”

NK cell-based therapies for HIV infection: Investigating current advances and future possibilities

“…The minor proportion of circulating NK cells are CD3 – CD56 bright CD16 – NK cells, which are poorly cytolytic but specialized to secrete large quantities of pro‐inflammatory cytokines. Instead, CD3 – CD56 dim CD16 + NK cells comprise the majority of circulating NK cells and are highly cytotoxic 6 . It is important to note that these proportions are reversed in healthy secondary lymphoid tissues.…”

“…Interestingly, it has been reported that during active HIV replication there is a reduction in the number of CD3 – CD56 + NK cells and a concomitant rise in the CD3 – CD56 – CD16 + NK cell count within the peripheral circulation 95 . NK cells are already well known for their applications in cancer immunotherapy through the exploitation of their anti‐tumor properties 6 . However, recently there have been numerous clinical trials investigating the role of NK cell modulation in controlling HIV 7 .…”