Figure 1.

iNKT cell development. iNKT cells express PLZF upon positive selection and undergo a unique intrathymic maturation, expansion, and differentiation program. This includes multiple rounds of intrathymic cell divisions, the acquisition of a memory phenotype, the activation of Th1, Th2 and Th17 cytokine genes and the expression of a panoply of NKRs. Furthermore, iNKT cells branch into three polarized subsets, NKT1, NKT2, and NKT17 cells before egress into the periphery. In the periphery NKT1 cells home preferentially to the spleen and liver while NKT2 and NKT17 cells mainly populate the lung and peripheral lymph nodes, respectively. Although TCR signal strength has been implicated in the polarization of the three iNKT cell sublineages and the regulation of PLZF expression, the intrathymic branching traits and cellular and molecular mechanisms of sublineage diversification are still under investigation. NKR, NK lineage receptors including NK1.1, Ly49, NKG2D, CD94, DX5; PLZF, promyelocytic leukemia zinc finger.