Human thymus contains IFN-α-producing CD11c-, myeloid CD11c+, and mature interdigitating dendritic cells

Abstract

Three distinct dendritic cell (DC) subsets capable of stimulating allogeneic naive T cells were isolated from human thymus. The most abundant subset was represented by plasmacytoid DCs (pDCs), which secreted high amounts of IFN-α upon stimulation with inactivated influenza virus and thus likely correspond to the recently identified peripheral blood natural IFN-α/β-producing cells (IPCs). Like those latter cells, thymic pDCs had distinctive phenotypic features (i.e., Lin-, HLA-DRint, IL-3Rαhi, CD45RAhi, CD11c-, CD13-, and CD33lo) and developed into mature DCs upon culture in IL-3 and CD40L. Of the two other DC subsets, one displayed a phenotype of immature myeloid DCs (imDCs) (HLA-DRint, CD11c+, CD13+, CD33+), and the other represented HLA-DRhi CD11c+ mature DCs (mDCs). Since they also expressed DC-LAMP, these mDCs appear to correspond to interdigitating dendritic cells (IDCs). Thymic pDCs, but not myeloid imDCs, strongly expressed lymphoid-specific transcripts such as pre-Tα, λ-like, and Spi-B, thereby suggesting a possible lymphoid origin. The detection of Spi-B mRNA, not only upon in vitro maturation of pDCs, but also in freshly purified IDCs, suggests that in vivo pDCs may differentiate into IDCs.