Lymphocytes and dendritic cells (DCs) are critical for immune response
s, yet how they develop from pluripotent hematopoietic stem cells is p
oorly defined. In humans and mice, it is possible to isolate phenotypi
cally defined subsets of bone marrow (BM) cells that represent interme
diate progenitors without long-term repopulating characteristics but w
ith specific lineage differentiation properties. For instance, murine
BM CD34(+) CD45RA(+) cells are progenitors for B and T lymphocytes wit
h no in vivo repopulation activity. In human BM, a small subset (5%) o
f cells having the phenotype CD34(+) Lin(-) CD10(+) CD45RA(+) CD38(+)
Thy-1(-) c-kit(-) represents a new class of hematopoietic progenitor c
ells that gives rise to lymphocytes [T, B, and natural killer (NK) cel
ls] and to DCs but does not produce myeloid or erythroid cells. The id
entification of such progenitor cells provides the opportunity to defi
ne the differentiation and growth requirements for the production of l
ymphocytes and DCs. Genes involved in lineage specification can also b
e studied. Altogether, these studies have fundamental implications for
understanding the biology of pivotal lineages of immune cells. This u
nderstanding could be used to treat a variety of immunodeficiencies an
d to design novel immunotherapies particularly in the context of hemat
opoietic cell transplantation.