The role of hematogenous and intrinsic precursor cells in lymphocyte production in murine bone marrow and thymus

Abstract

It is well recognized that the bone marrow contains cells that can repopulate a depleted thymus as well as cells that can be induced to express phenotypic markers characteristic of T cells. It is not known, however, to what extent thymocytopoiesis in the normal thymus relies on immigrant, bone marrow-derived cells, nor whether some T cell precursors have entered the bone marrow from the circulation. We used the parabiotic system to test whether thymocytopoiesis relies on progenitors intrinsic to the thymus or on cells that enter the organ from the circulation. In the same system, we have also investigated whether Thy-1- bone marrow lymphocytes that respond to phytohemagglutinin (PHA) by proliferation and Thy-1 expression are produced by myelogenous or hematogenous progenitors. Syngeneic CBA/HT6 and CBA/CaJ mice were joined in parabiotic union at 4-6 weeks of age. Cross circulation between the two partners was verified by the equilibration of Evans' blue dye injected into one partner and by the equilibration of PHA-responsive T cells in the spleen of the parabionts. Chromosome spreads were prepared from the PHA-stimulated T cell-depleted bone marrow and from spontaneously proliferating thymocytes as well as from thymocytes stimulated by PHA or Concanavalin A (Con A). The exchange of spleen colony-forming units (CFU-S) in the femoral marrow was assessed by karyotyping individual spleen colonies. Regardless of the length of parabiotic union, ranging from 4 to 20 weeks, Thy-1-, PHA-responsive bond marrow lymphocytes remained predominantly of the host type with only 3% being derived from the opposite partner.(ABSTRACT TRUNCATED AT 250 WORDS)

Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure

“…We cannot, however, exclude the possibility that HSCs that have recently transited blood compete less effectively in the reconstitution (transplantation) assay used for their detection because it is possible that the homing defect described in mobilized cells 18,26 persists after their return from blood to marrow. Do the number of partner HSCs in marrow plateau or increase slowly over time, as suggested by our studies (Table 1) and by those of Mejino et al 7 and Wright et al, 11 or is the increment more dramatic (24% at 6-7 months), as recently reported by Wagers et al 27 using a related experimental design? Are results strain-specific?…”

“…3 Parabiosis has been used to demonstrate the existence of hormones 4,5 and to analyze lymphocyte trafficking. 6,[7][8][9] In early hematopoietic studies, Warren et al 10 linked a healthy rat to a lethally irradiated partner. Hematopoiesis was restored in the irradiated partner, and its marrow showed normal cellularity when studied at 14 weeks.…”

“…Others have studied the transfer of hematopoietic cells between phenotypically distinct healthy (ie, nonirradiated) parabionts. Harris et al 9 showed that 5% of mitotic cells in marrow had a partner cytogenetic phenotype after 4 to 5 weeks of parabiosis; Mejino et al 7 showed a stable low (5%) level of partner spleen cell colony-forming unit (CFU-S) after 5 and 15 weeks of parabiosis; and Wright et al 11 demonstrated that there was little (0%-9%) transfer of Thy1.1 low , lineage-negative, Sca-1 ϩ , c-kit ϩ cells, a population inclusive of HSCs, after 7, 16, or 39 weeks of parabiosis. In our studies, ROSA26 and PeP3 b mice, congenic on a C57BL6 background, were used to create parabiotic pairs.…”