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J Immunol
2014[Jul]; 193
(1
): 21-5
PMID24890722
show ga
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.