Cutting Edge: Antigen-Specific Thymocyte Feedback Regulates Homeostatic Thymic Conventional Dendritic Cell Maturation

Abstract

Thymic dendritic cells (DC) mediate self-tolerance by presenting self-peptides to and depleting autoreactive thymocytes. Despite a significant role in negative selection, the events regulating thymic DC maturation and function under steady-state conditions are poorly understood. We report that cross-talk with thymocytes regulates thymic conventional DC (cDC) numbers, phenotype, and function. In mice lacking TCR-expressing thymocytes, thymic cDC were reduced and exhibited a less mature phenotype. Furthermore, thymic cDC in TCR-transgenic mice lacking cognate Ag expression in the thymus were also immature; notably, however, thymic cDC maturation was re-established by an Ag-specific cognate interaction with CD4+ or CD8+ single-positive thymocytes (SP). Blockade of CD40L during Ag-specific interactions with CD4 SP, but not CD8 SP, limited the effect on cDC maturation. Together, these novel findings demonstrate that homeostatic maturation and function of thymic cDC are regulated by feedback delivered by CD4 SP and CD8 SP via distinct mechanisms during a cognate Ag–specific interaction.