Thymocytopoiesis is Maintained by Blood-borne Precursors Throughout Postnatal Life. A Study in Parabiotic Mice

This study was designed to resolve the long standing controversy as to whether hematogenous precursors or resident intrathymic precursors maintain thymocytopoiesis in postnatal life. The kinetics of thymic chimerism was examined over a 21-wk period in 105 pairs of nonirradiated, Thy-1-alloantigen-disparate, parabiotic B10.S mice. Thymic chimerism reached reached maximum levels of 25% in the Thy-1b and 16% in the Thy-1a partners (mean 20.5% and 9.8%, respectively) 6 to 7 wk after parabiotic union. Most of the donor-origin thymocytes were located in the thymus cortex and expressed high levels of Thy-1 Ag and terminal deoxynucleotidyl transferase. Thymic chimerism did not reach 50% because circulating prothymocytes, unlike peripheral T cells, do not distribute randomly in the blood of parabiotic partners. This was shown in irradiated pairs of Thy-1-alloantigen-identical parabiotic mice, one member of which was injected i.v. with Thy-1-alloantigen-disparate bone marrow cells. Only 10% of the total donor-origin prothymocyte activity was detected in the opposite parabiont 72 h later. Similarly, the level of thymic chimerism in nonirradiated, Thy-1-alloantigen-disparate parabionts closely corresponded to the donor: host ratio of prothymocytes in the blood (i.e., between 10 and 20%), as determined directly by an intrathymic adoptive transfer assay. The continued dependence of thymic chimerism on blood-borne precursors was formally demonstrated by surgically separating mice 9 wk after parabiosis. Twelve weeks later, thymic chimerism was 50 to 80% lower in the separated parabionts than in sham-operated controls. The possible role of "stress" in initiating or maintaining thymic chimerism during parabiosis appeared to be excluded by the existence of similar kinetics of thymocytopoiesis (including the onset of thymic involution) in parabiotic and nonparabiotic mice; and by the occurrence of similar levels of thymic chimerism in adrenalectomized and nonadrenalectomized parabiotic mice. Thus these experiments demonstrate that the maintenance of thymocytopoiesis in postnatal life, as in prenatal life, is primarily dependent upon blood-borne prothymocytes, and that intrathymic precursors are replaced at an average rate of 2 to 3%/day.