Invariant natural killer T cells: front line fighters in the war against pathogenic microbes

Abstract

Invariant natural killer T (iNKT) cells constitute a unique subset of innate-like T cells that have been shown to have crucial roles in a variety of immune responses. iNKT cells are characterized by their expression of both NK cell markers and an invariant T cell receptor (TCR) α chain, which recognizes glycolipids presented by the MHC class I-like molecule CD1d. Despite having a limited antigen repertoire, the iNKT cell response can be very complex, and participate in both protective and harmful immune responses. The protective role of these cells against a variety of pathogens has been particularly well documented. Through the use of these pathogen models, our knowledge of the breadth of the iNKT cell response has been expanded. Specific iNKT cell antigens have been isolated from several different bacteria, from which iNKT cells are critical for protection in mouse models. These responses can be generated by direct, CD1d-mediated activation, or indirect, cytokine-mediated activation, or a combination of the two. This can lead to secretion of a variety of different Th1, Th2, or Th17 cytokines, which differentially impact the downstream immune response against these pathogens. This critical role is emphasized by the conservation of these cells between mice and humans, warranting further investigation into how iNKT cells participate in protective immune responses, with the ultimate goal of harnessing their potential for treatment.

Donor-unrestricted T cells in the human CD1 system

“…The deletion of NKT cells in mice by knockout of CD1d- or TCR-joining regions results in many altered immunological outcomes in vivo in mice, a topic that has been reviewed in detail (Barral and Brenner 2007) and considered in another chapter of this issue (Crosby and Kronenberg 2016). Invariant NKT cells are less abundant in humans as compared to mice, but their activation and function has been examined by the use of α-galactosyl ceramide analogs in pre-clinical cancer studies.…”

Enhanced oxidative phosphorylation in NKT cells is essential for their survival and function

“…In the peripheral organs like liver, spleen, lymph node, and adipose tissue, NKT cells differentiate further and gain specific functional characteristics to become proinflammatory or immunomodulatory (10). Thus, NKT cells are a heterogeneous population that show a high degree of phenotypic and functional specialization and their role in autoimmune diseases (11,12), infectious diseases (13)(14)(15), asthma (16), and antitumor immune responses in both experimental models and humans (10,(17)(18)(19) has been well established.…”

Differing roles of CD1d2 and CD1d1 proteins in type I natural killer T cell development and function

“…Chronic stimulation by these "autoantigens" leads some type I NKT cells to produce cytokines at steady state, which, in turn, influences the development and activation of surrounding cells (16,17). Thus, their unique properties establish type I NKT cells as important regulators of immune responses and tissue homeostasis (18).…”