دانلود رایگان مقاله انگلیسی منشاء حافظه سلول کشنده طبیعی: آفرینش خاص یا سازگاری تکاملی - وایلی 2018

Summary

The few initial formative studies describing non-specific and apparently spontaneous activity of natural killer (NK) cells have since multiplied into thousands of scientific reports defining their unique capacities and means of regulation. Characterization of the array of receptors that govern NK cell education and activation revealed an unexpected relationship with the major histocompatibility molecules that NK cells originally became well known for ignoring. Proceeding true to form, NK cells continue to upend archetypal understanding of their ever-expanding capabilities. Discovery that the NK cell repertoire is extremely diverse and can be reshaped by particular viruses into unique subsets of adaptive NK cells challenges, or at least broadens, the definition of immunological memory. This review provides an overview of studies identifying adaptive NK cells, addressing the origins of NK cell memory and introducing the heretical concept of NK cells with extensive antigenic specificity. Whether these newly apparent properties reflect adaptive utilization of known NK cell attributes and receptors or a specially creative allocation from an undefined receptor array remains to be fully determined.

Concluding remarks

Ample evidence has accumulated that NK cells proliferate, mature and differentiate in response to various environmental cues. These responses transform the naive NK cell repertoire, which already varies with host genetic background, into a mature repertoire adapted in terms of activating and self-specific KIR expression, Ctype lectin-like receptor expression, CD16 expression, maturation markers, intracellular signalling molecules and transcription factors. Although this constitutes a memory population of immune effector cells, only in the case of MCMV is there definitive evidence of a mechanism for selective expansion of NK cells with specificity for a particular antigen. A limited number of examples in mice and macaques hint at the possibility of antigen specificity involving an NK cell activating receptor repertoire beyond that currently known, but evidence for the nature of a receptor repertoire specially created for NK cell adaptive responses is lacking. Hence, some ambivalence still exists as to the perceived nature of NK cell memory. In the clearest examples, there is monochromatic recognition of select foreign proteins and non-specific cytokines that enhance secondary effector function. Still to be fully explained is the NK cell antigen specificity similar to that bestowed by clonotypic receptors reported in mice and peptide or other modification of NK cell receptor ligands that tilt the balance towards activation of NK cells with particular receptor constellations. In the latter case, memory for any particular pathogen would reflect collective recognition of multiple ligands with signal integration triggering a select set of NK cells to proliferate and differentiate in a manner that lowered the threshold for activation upon secondary exposure to the same set of environmental cues. This possibility requires only subtle extension of what is already accepted about integration of positive and negative signals to control NK cell activation. A more speculative possibility would be collective memory of specific environmental cues distributed among a network of NK cells, rather than attributable to single antigen-specific cells. In this scenario, NK cells would have evolved to provide context-dependent help through intercellular communications in a manner similar to the establishment of memory with neuronal networks. Much remains to be explained regarding the unanticipated behaviour of NK cells revealed over the last two decades. The massive implications for basic and translational science will continue to drive research on NK cell memory that promises more surprises.