Making memory at birth: understanding the differentiation of natural killer T cells

Abstract

Glycolipid reactive natural killer T cells with an invariant TCR α-chain (iNKT cells) are a conserved population of T lymphocytes with a distinct anatomical distribution and functional properties. The differentiation pathway of iNKT cells branches off from mainstream thymocyte differentiation at the double positive stage, and recent work has revealed how signaling events early in the iNKT cell pathway imprint a memory-like behavior on these cells. Additionally, unique molecular interactions governing iNKT cell development and tissue distribution have been uncovered recently, building up our knowledge of the complex network of interactions that form this population. Novel autologous antigens for these cells have been identified, although it has not yet been resolved if there is single endogenous antigen responsible for both positive selection and/or peripheral activation.

Figure 1

Diagram showing approximate limits of accessibility of the TCR Jα locus to rearrangement at early and late stages of the lifespan of a DP thymocyte, the developmental potential of early and late DP thymocytes with respect to conventional and Vα14i NKT differentiation, and some factors known to regulate DP lifespan. The position of the Jα18 segment that is required for formation of the invariant NKT TCR is indicated in bold type. Secondary rearrangements occur if the primary rearrangement does not support positive selection. The exact boundary of rearrangement in early DP thymocytes is uncertain, and more likely represents a gradient of accessibility, with distal Jα rearrangements occurring in longer lived DP thymocytes. [17]