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Blood, 15 April 2002, Vol. 99, No. 8, pp. 2948-2956
IMMUNOBIOLOGY
Identification of a myeloid intrathymic pathway of dendritic cell
development marked by expression of the granulocyte
macrophage-colony-stimulating factor receptor
Virginia G. de Yébenes,
Yolanda R. Carrasco,
Almudena
R. Ramiro, and
María L. Toribio
From the Centro de Biología Molecular "Severo
Ochoa," CSIC, Facultad de Biología, Universidad
Autónoma de Madrid, Spain.
In this study, the finding that a significant proportion of all
dendritic cells (DCs) resident in vivo in the human postnatal thymus
displayed a myeloid-related phenotype prompted us to re-examine the
developmental origin of thymic DCs, a cell type hitherto considered to
represent a homogeneous lymphoid-derived population. We show here that
these novel intrathymic DCs are truly myeloid, as they arise from
CD34+ early thymic progenitors through CD34lo
intermediates which have lost the capacity to generate T cells, but
display myelomonocytic differentiation potential. We also demonstrate
that phenotypically and functionally equivalent myeloid precursors
devoid of T-cell potential do exist in vivo in the postnatal thymus.
Moreover, although interleukin 7 (IL-7) supports the generation of such
myeloid intermediates, we show that their developmental branching from
the main intrathymic T-cell pathway is linked to the up-regulation of
the myelomonocytic granulocyte macrophage-colony-stimulating factor
(GM-CSF) receptor, to the down-regulation of the IL-7 receptor and to
the lack of pre-T-cell receptor  (pT) gene transcriptional
activation. Taken together, these data challenge the current view that
the thymus is colonized by a lymphoid-restricted progenitor and provide
evidence that a more immature precursor population with lymphoid and
myelomonocytic potential is actually seeding the human postnatal thymus.
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