Abstract
Invariant natural killer T (iNKT) cells are a unique T cell lineage that develop in the thymus and emerge with a memory-like phenotype. Accordingly, following antigenic stimulation, they can rapidly produce copious amounts of Th1 and Th2 cytokines and mediate activation of several immune cells. Thus, it is not surprising that iNKT cells play diverse roles in a broad range of diseases. Given their pivotal roles in host immunity, it is crucial that we understand the mechanisms that govern iNKT cell development and effector functions. Over the last two decades, several studies have contributed to the current knowledge of iNKT cell biology and activity. Collectively, these studies reveal that the thymic development of iNKT cells, their lineage expansion, and functional properties are tightly regulated by a complex network of transcription factors and signaling molecules. While prior studies have clearly established the importance of the SLAM-SAP-Fyn signaling axis in iNKT cell ontogenesis, recent studies provide exciting mechanistic insights into the role of this signaling cascade in iNKT cell development, lineage fate decisions, and functions. Here we summarize the previous literature and discuss the more recent studies that guide our understanding of iNKT cell development and functional responses.
Highlights
Conventional T cells (Tcon) develop in the thymus and are characterized by the presence of a diverse spectrum of T cell antigen receptors (TCRs) that recognize a wide array of peptide antigens
Employing cells or mice that either expressed the wild-type or a mutant version of SAP that cannot bind to Fyn (SapR78A), we demonstrated that the SAP-Fyn interaction is critical for efficient Invariant natural killer T (iNKT) cell development in vitro as well as in vivo [77]
Clinical success of gene therapy will require careful selection of the safest and most efficient viral vectors to ensure effective transfer of the corrected gene without inducing harmful mutagenesis. It has been over three decades since the “unconventional” NK1.1+TCRβ+ T cells were first described, but it is only in the last 15 years that we have really begun to gain deeper insights into the complex network of transcription factors and signaling molecules that modulate iNKT cell development and function
Summary
Conventional T cells (Tcon) develop in the thymus and are characterized by the presence of a diverse spectrum of T cell antigen receptors (TCRs) that recognize a wide array of peptide antigens. There exist several subsets of T lymphocytes that develop in the thymus but do not recognize peptide antigens, have limited TCR expression, and are relatively rare in number when compared to Tcon Despite their lower incidence, most of these “unconventional” T cells are fast responders to antigenic stimulation and play pivotal roles in host immune responses. Most of these “unconventional” T cells are fast responders to antigenic stimulation and play pivotal roles in host immune responses Some of these atypical T cells include but are not limited to CD1-restricted natural killer T (NKT), MR1-restricted mucosal associated invariant T (MAIT), and γδ T cells. We review our current knowledge of invariant NKT cells focusing on the role of SLAM-SAP-Fyn signals in their development and function
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