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Blood, Vol. 95 No. 3 (February 1), 2000: pp. 879-885

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

Anastasia Guerriero, Peter B. Langmuir, Lisa M. Spain, and Edward W. Scott

From the Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, PA, and the Wistar Institute, Philadelphia, PA.

The ets-family transcription factor PU.1 is required for the proper development of both myeloid and lymphoid progenitors. We used PU.1-deficient animals 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+ CD8alpha + DEC-205+. But they lack myeloid-derived DC: low-density MHC-II+ CD11c+ CD8alpha - DEC-205-. PU.1-/- embryos also lack progenitors capable of differentiating into myeloid DC in response to granulocyte-macrophage colony-stimulating factor plus interleukin-4. The appearance of lymphoid DC in developing PU.1-/-thymus was initially delayed, but this population recovered to wild type (WT) levels upon organ culture of isolated thymic lobes. PU.1-/-lymphoid DC were functionally equivalent to WT DC for stimulating T-cell proliferation in mixed lymphocyte reactions. These results demonstrate that PU.1 is required for the development of myeloid DC but not lymphoid DC.


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