Long-term multilineage chimerism, indicating pluripotent hematopoietic
stem cell engraftment, was achieved in an Ly5-congenic strain combina
tion without irradiation or other host conditioning when a large numbe
r of donor marrow cells (1.4-2x10(8)) was administered. However, the i
nitial (2-4 weeks posttransplantation) percentages of T and B lymphocy
tes of donor origin were markedly lower than those of myeloid lineages
. Steady-state levels of donor and host repopulation of all lineages w
ere reached by 7 to 15 weeks posttransplantation and remained relative
ly constant for at least 41 weeks. B cell chimerism was similar to tha
t seen in myeloid lineages at steady state. In contrast, long-term don
or representation in the T cell lineage was much lower than in the B c
ell or myeloid lineages. Host treatment with depleting anti-T cell mon
oclonal antibodies increased the donor contribution to early T cell re
population, but long-term T cell chimerism was still significantly low
er in all lymphohematopoietic tissues, including the thymus, than B ce
ll or myeloid cell chimerism. Pretreatment of hosts with 3.5 Gy of loc
al irradiation to the thymic region further increased the donor contri
bution to initial T cell repopulation, which equaled that of other lin
eages at 4 to 7 weeks. However, donor representation in the T cell lin
eage declined by the time steady-state chimerism was attained and was
lower than donor representation in the B cell or myeloid lineages. A h
igher dose of thymic irradiation (7 Gy) led to a reduction in this dis
crepancy, so that levels of donor thymopoiesis and hematopoiesis in ot
her lineages were similar by 23 to 27 weeks posttransplantation. The d
ifferential contribution of adult donor marrow to long-term, steady-st
ate thymopoiesis vs. hematopoiesis in other lineages under certain con
ditions in this competitive repopulation assay suggests that functiona
lly distinguishable progenitors are responsible for these activities.