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Divisions of
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Immunology, Allergy, and Infectious Diseases and
General Dermatology, Department of Dermatology, University of Vienna Medical School, Vienna, Austria
Langerhans cells (LC) are CD1a+E-cadherin
(E-cad)+Birbeck granule+ but
CD11b-CD36-factor XIIIa
(FXIIIa)- members of the dendritic cell (DC) family.
Evidence holds that LC originate from
CD1a+CD14- rather than
CD14+CD1a- progenitors, both of which arise
from GM-CSF/TNF-
-stimulated CD34+ stem cells. The
CD14+CD1a- progenitors, on the other hand, can
give rise to a separate DC type characterized by its
CD1a+CD11b+CD36+FXIIIa+E-cad-BG-
phenotype (non-LC DC). Although GM-CSF/TNF- are important for both
LC and non-LC DC differentiation, TGF-ß1 is thought to preferentially
promote LC development in vitro and in vivo. However, the hemopoietic
biology of this process and the nature of TGF-ß1-responsive LC
precursors (LCp) are not well understood. Here we show that
CD14+ precursors in the presence, but not in the absence,
of TGF-ß1 give rise to a progeny that fulfills all major criteria of
LC. In contrast, LC development from CD1a+ progenitors was
TGF-ß1 independent. Further studies revealed that CD14+
precursors contain a CD11b+ and a CD11b-
subpopulation. When either subset was stimulated with GM-CSF/TNF-
and TGF-ß1, only CD14+CD11b- cells
differentiated into LC. The CD11b+ cells, on the other
hand, acquired non-LC DC features only. The higher doubling rates of
cells entering the CD14+ LCp rather than the
CD1a+ LCp pathway add to the importance of
TGF-ß1 for LC development. Because
CD14+CD11b- precursors are multipotent cells
that can enter LC or macrophage differentiation, it is suggested that
these cells, if present at the tissue level, endow a given organ with
the property to generate diverse cell types in response to the local
cytokine milieu.
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