Blood, 1 June 2001, Vol. 97, No. 11, pp. 3325-3326
Parentage and heritage of dendritic cells
Dendritic cells (DCs), despite their common functions of
antigen-processing and T-lymphocyte activation, are diverse in surface markers, migratory patterns, and cytokine output. These differences can
determine the fate of the T cells they activate. But tracing the
ancestry of these specialized DC subtypes has proved to be a dubious
enterprise. The original concept that all DCs were of myeloid origin
was questioned when Ardavin et al (Nature. 1993;362:761-763) found a
mouse thymus T precursor population, which although lacking a capacity
to form macrophages or granulocytes, produced thymic DCs. Since these
DCs also expressed some lymphoid markers, including CD8
, they were
termed "lymphoid DCs." It was assumed that murine DC lacking CD8
and expressing certain myeloid markers would be the product of myeloid
precursors; so these were termed "myeloid DCs." But our assumption
that the early hemopoietic precursor determined the mature DC phenotype
was upset when Traver et al (Science. 2000;290:2152-2154) found that
bone-marrow myeloid-restricted precursors produced both
CD8+ and CD8
DCs. Manz et al (page
3333) now complete the picture, demonstrating that lymphoid-restricted
precursors are indeed efficient producers of DCs but that both
lymphoid-restricted and myeloid-restricted precursors are able to
generate both CD8+ and CD8 DCs. These
results from the Stanford laboratory are in close agreement with our
own current findings (Wu and D'Amico, in preparation). Manz et al
argue that, since myeloid precursors outnumber lymphoid precursors,
most DCs will be of myeloid origin; however, this balance will depend
on the relative efficiency of the 2 precursors at generating DCs, on
the kinetics of development, and on local environmental influences.
Does this early developmental flexibility mean the ancestry of DCs is
irrelevant and that different DC subtypes simply represent different
activation states? Not quite. The mature DC subtypes are not readily
interconvertible. Recent kinetic evidence (Kamath et al, J
Immunol. 2000;165:6762-6770) indicates that the DC subtypes of spleen
are the products of separate developmental streams, at least as far
back as their immediate dividing precursors. We must now determine the
points downstream of the conventional myeloid and lymphoid precursors
where the DC sublineages branch off, and determine the cytokines and
environmental factors that induce their specialized functions.
Ken Shortman and Li Wu
The Walter and Eliza Hall Institute
