"Natural Regulators": NK Cells as Modulators of T Cell Immunity

Abstract

Natural killer (NK) cells are known as frontline responders capable of rapidly mediating a response upon encountering transformed or infected cells. Recent findings indicate that NK cells, in addition to acting as innate effectors, can also regulate adaptive immune responses. Here, we review recent studies on the immunoregulatory function of NK cells with a specific focus on their ability to affect the generation of early, as well as long-term antiviral T cell responses, and their role in modulating immune pathology and disease. In addition, we summarize the current knowledge of the factors governing regulatory NK cell responses and discuss origin, tissue specificity, and open questions about the classification of regulatory NK cells as classical NK cells versus group 1 innate lymphoid cells.

Keywords: ILC; NK cells; adaptive immunity; immune regulation; viral infection.

Figure 1

NK cell regulation of T cell immunity. NK cells can modulate the activities of T cells either indirectly, by eliminating, or affecting the functions of antigen-presenting cells, especially DCs, or through direct interactions with T cells themselves. During viral infections, these regulatory interactions can lead to differing outcomes depending on the infecting viral pathogen and the phase of the infection. During acute infection, NK cell regulation can dampen antiviral T cell responses (, –11), lead to increased viral loads (–11), and ultimately determine the extent of pathology in tissues (9, 10). In infections that have a chronic phase, NK cells can determine the longevity of the infection and indeed extend it (7, 11, 12, 33, 36). Memory T cell responses are generated at reduced frequencies (30), and antibody responses can be compromised due to impaired formation of germinal centers (30, 36). This apparently incongruous dampening of immune response is reconciled by the finding that curbing chronic immune responses following viral infections is critical to reducing the development of autoimmunity (12).