SEPARATE REGULATION OF PERIPHERAL HEMATOPOIETIC AND THYMIC ENGRAFTMENT

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.