Human thymus contains IFN-alpha-producing CD11c(-), myeloid CD11c(+) and mature interdigitating dendritic cells

Three distinct dendritic cell (DC) subsets capable of stimulating allogenei c naive T cells were isolated from human thymus. The most abundant subset w as represented by plasmacytoid DCs (pDCs), which secreted high amounts of I FN-alpha upon stimulation with inactivated influenza virus and thus likely correspond to the recentlyidentified peripheral blood natural IFN-alpha/bet a -producing cells (IPCs). Like those latter cells, thymic pDCs had distinc tive phenotypic features (i.e., Lin(-), HLA-DRint, IL-3R alpha (hi), CD45RA (hi), CD11c(-), CD13-, and CD3310) and developed into mature DCs upon cultu re in IL-3 and CD40L. Of the two other DC subsets, one displayed a phenotyp e of immature myeloid DCs (imDCs) (HLA-DRint, CD111c(+), 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 expres sed lymphoid-specific transcripts such as pre-T alpha, lambda -like, and Sp i-B, thereby suggesting a possible lymphoid origin. The detection of Spi-B mRNA, not only upon in vitro maturation ofpDCs, but also in freshly purifie d IDCs, suggests that in vivo pDCs may differentiate into IDCs.