Abstract
Natural killer (NK) cells play a significant and vital role in the first line of defense against infection through their ability to target cells without prior sensitization. They also contribute significantly to the activation and recruitment of both innate and adaptive immune cells through the production of a range of cytokines and chemokines. In the context of cytomegalovirus (CMV) infection, NK cells and CMV have co-evolved side by side to employ several mechanisms to evade one another. However, during this co-evolution the discovery of a subset of long-lived NK cells with enhanced effector potential, increased antibody-dependent responses and the potential to mediate immune memory has revolutionized the field of NK cell biology. The ability of a virus to imprint on the NK cell receptor repertoire resulting in the expansion of diverse, highly functional NK cells to this day remains a significant immunological phenomenon that only occurs in the context of CMV. Here we review our current understanding of the development of these NK cells, commonly referred to as adaptive NK cells and their current role in transplantation, infection, vaccination and cancer immunotherapy to decipher the complex role of CMV in dictating NK cell functional fate.
Highlights
Cytomegalovirus (CMV) has an interesting and diverse relationship with the human immune system, co-evolving side by side for millions of years to produce a finely tuned symbiotic relationship under normal homeostatic conditions
In recipients who received a transplant from a CMV+ donor, we demonstrated the potential of NKG2C+ Natural killer (NK) cells to represent memory-like NK cells with heightened effector function and expansion following CMV reactivation
Rather activating receptors such as DNAX accessory molecule-1 (DNAM-1) or NKG2D are likely involved [99]. This suggests that while NKG2C marks adaptive NK cells, its contribution to the recognition and elimination of cancer cells remains unclear. In support of this we have recently demonstrated that while NKG2C+ adaptive NK cells were associated with increased effector function against B cell acute lymphoblastic leukemia (ALL), NKG2C recognition of human leukocyte antigen (HLA)-E was not involved in this increased function [100]
Summary
Cytomegalovirus (CMV) has an interesting and diverse relationship with the human immune system, co-evolving side by side for millions of years to produce a finely tuned symbiotic relationship under normal homeostatic conditions. While immunocompetent individuals rarely present with symptoms, CMV infection remains a serious threat to immunocompromised individuals such as transplant recipients and is the most common congenital infection that can lead to significant neurological deficiencies in newborns [1]. Natural killer (NK) cells play an important role in combating CMV infection, which has resulted in a dynamic interplay between NK cells and CMV evasion mechanisms. To date only identified in the context of CMV infection, the discovery of these NK cells has played a significant role in advancing our understanding of NK cell function and their ability to bridge the divide between innate and adaptive immune responses. Adaptive NK cells have emerged as important players across several contexts from viral infections and vaccination to transplantation and cancer immunotherapy
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