Natural T_H17 cell development in the thymus

Recently, CD4⁺ single positive (SP) thymocytes that express retinoic acid receptor-related orphan receptor-γt (RORγt) and secrete interleukin-17 (IL-17) were identified (natural T_H17 cells). This study describes the requirements for the development of natural T_H17 cells. Unlike conventional CD4⁺ SP thymocytes and peripheral T_H17 cells, IL-17-producing CD4⁺ SP thymocytes showed a skewed expression of the Vβ3 T cell receptor (TCR) chain. Interestingly, MHC class II expression on medullary but not cortical thymic epithelial cells was necessary for the development of natural T_H17 cells. Moreover, defective TCR signalling (owing to a mutation in the gene encoding the TCR signalling adaptor SLP76) resulted in increased numbers of natural T_H17 cells in the thymus, but blocked the differentiation of peripheral CD4⁺ T cells into effector T_H17 cells in the intestine, suggesting that these two IL-17-producing T cell populations are distinct.