Thymic control of proliferation of T cell precursors in bone marrow.

Abstract

The activity of.T lymphocyte precursors (pre-T cells) in the bone marrow of mice was measured by the concanavalin A response synergy assay. Pre-T cell levels were low in marrow of neonatally thymectomized mice and could be restored to control values by treatment in vivo with an extract of mouse thymus. Levels of activity were also low in aging mice and again could be restored by thymic extract treatment. The most profound fall with ang was in the proliferating pre-T cell compartment as detected bytritiated thymidine suicide; and this compartment was restored by thymic extract treatment. Irradiation to the thymus, with the bone marrow shielded, caused a fall in resting pre-T cells in the bone marrow and a concomitant rise in proliferating cells. These results are consistent with a model of control of pre-T cell maturation in which the thymus senses the number of developing iymphocytes within it and responds to a fall in this number by increasing production of hormone. The hormone acts on resting pre-T cells in the marrow, stimulating some of them to proliferate, leave the bone marrow, and repopulate the thymus.

In Vitro Culture During Retroviral Transduction Improves Thymic Repopulation and Output After Total Body Irradiation and Autologous Peripheral Blood Progenitor Cell Transplantation in Rhesus Macaques

“…The most likely pathway for the generation of T‐cells is the thymic‐dependent pathway in this group, which was supported by less peripheral expansion of T‐cells, higher TREC levels, and preserved thymic architecture [39, 40]. The observed differences between the groups could be due to thymic production of naïve T‐cells induced by feedback signals from the T‐cell depleted periphery, therefore inducing higher thymic activity [41, 42]. The highest numbers of DCs and monocytes were also observed in the selected‐transduced group, which may also have an impact on T‐cell homeostasis, as APCs enhance induction of T‐cell activation and proliferation in the periphery.…”

Modulation of Mouse Natural Killer Cell Activity by the Serum Thymic Factor

“…In addition to their clfect on T-cell maturation, thymic hormones have been shown to play a role in the induction of proliferation of pre-T cells in the bone marrow [5], In this case, the matunitton of thymic cells, which would tend to decrease N K activity secondarily, could be overpowered by the efTecc of FTS on the bone tnarrow. leading to the seeding of a large number of prc-T cells in ihc pcripliery.…”

Influence of thymic genotype on the systemic lupus erythematosus-like disease and T cell proliferation of MRL/Mp-lpr/lpr mice.

“…Our experiments have not established whether the T cell defect associated with the disease is acquired at the prethymic or thymic level. Nor have they determined whether the thymic effects necessary for expression of T cell proliferation are exerted within the thymic microenvironment or extrathymically via thymic hormones (15), or both. Nevertheless these experiments certainly exclude causation of the disease by intrinsic abnormalities of the lpr/lpr thymus (hormonal or microenvironmental) because the lpr/lpr early, severe SLE is not prevented or delayed by +/+ thymus and transplantation of lpr/lpr thymus to the +/+ mice does not cause T cell proliferation and early SLE in this substrain.…”