PU.1 is required for myeloid-derived but not lymphoid-derived dendritic cells

The ets-family transcription factor PU.1 is required for the proper develop ment of both myeloid and lymphoid progenitors. We used PU.1-deficient anima ls to examine the role of PU.1 during dendritic cell development. PU.1(-/-) animals produce lymphoid-derived dendritic cells (DC): low density class II major histocompatibility complex [MHC-II+] CD11c(+) CD8 alpha(+) DEC-205(), But they lack myeloid-derived DC: low-density MHC-II+ CD11c(+) CD8 alpha (-) DEC-205(-). PU.1(-/-) embryos also lack progenitors capable of differen tiating into myeloid DC in response to granulocyte-macrophage colony-stimul ating factor plus interleukin-4. The appearance of lymphoid DC in developin g PU.1(-/-)thymus was initially delayed, but this population recovered to w ild type (WT) levels upon organ culture of isolated thymic lobes, PU.1(-/-) lymphoid DC were functionally equivalent to WT DC for stimulating T-cell pr oliferation in mixed lymphocyte reactions. These results demonstrate that P U.1 is required for the development of myeloid DC but not lymphoid DC. (C) 2000 by The American Society of Hematology.