Figure 1.

iNKT cells undergo metabolic switching during development and differentiation to meet their changing energy demands. iNKT cells originate from CD4⁺CD8⁺ double positive (DP) thymocytes that express the invariant TCR. They are positively selected by CD1d-expressing DP thymocytes. Immature iNKT cells from DP thymocytes undergo four maturation stages characterized by differential surface expression of CD24, CD44, and NK1.1. Proliferation rate and energy demands decrease as iNKT cells progress from stages 0 and 1 to the more quiescent stages 2 and 3. This transition is accompanied by increased autophagy. Ablation of autophagy genes Atg5, Atg7, or Vps34 in iNKT cells leads to defects in the transition to a quiescent state after population expansion of thymic iNKT cells.