Studies on the Role of the Thymus in Immunobiology

Abstract

The immunologic competence of spleen cells of mice, as assessed by their graft versus host capabilities, increases to 35 days of age and beyond. Thymectomy at any point along this continuum of development produces "immunologic arrest;" the peripheral lymphoid tissues of such mice do not show significant increases in activity as the animals mature, nor is there appreciable loss of activity up to 6 months after surgery. Adult spleen cells from mice thymectomized at 1 to 24 hours of age have a greatly reduced ability to induce runt disease. Five million spleen cells from immunologically mature animals will uniformly cause fatal runt disease in neonatal recipients, but this same number of cells from neonatally thymectomized animals produces almost no runt disease. When the dosage of cells from neonatally thymectomized C57Bl mice is increased to 20 million, about half of the A recipients develop runt disease. Thus, the defect is a quantitative one. Spleen cells from neonatally thymectomized mice will induce tolerance of skin grafts from the donor strain. In one recalcitrant strain combination, C57Bl to A, use of spleen cells from neonatally thymectomized donors as the tolerance-inducing inoculum permits survival of the recipients, which usually die with severe runt disease, but does not induce tolerance. Cell free extracts of spleen and thymus tissue, including "promine" of Szent-Gyorgyi et al., did not affect the runting syndrome or the immunologic reactivity of neonatally thymectomized mice. When syngeneic thymic tissue is grafted into neonatally thymectomized mice, or the animals are given viable syngeneic spleen or thymus cells, the majority of the animals escape the early mortality characteristic of this group. Administration of syngeneic spleen cells from adult donors and grafting of syngeneic neonatal thymus provide restoration of homograft immunity and graft versus host reactivity of the peripheral lymphoid tissues in most of the neonatally thymectomized animals. Thymus cells rarely provide significant restoration of these parameters. Allogeneic thymus grafts also restore neonatally thymectomized mice. Such animals are chimeric: the immunologically competent cells of their peripheral lymphoid tissues are chiefly of host origin as determined by the discriminant spleen assay, but in many instances a significant donor component is also demonstrable in this system. These chimeric animals accept skin grafts from both donor and host strains. A degree of reconstitution has also been attained by grafting of allogeneic adult spleen in neonatally thymectomized animals. The discriminant spleen assay indicates that cells of the donor strain predominate in the peripheral lymphoid tissues of such mice.

Human T Cell Development, Localization, and Function throughout Life

“…Human Treg cells also develop early in fetal life and are detected in thymii at 12 weeks and in LN at 14 weeks (Cupedo et al, 2005; Michaelsson et al, 2006). It was established some time ago that neonatal thymectomy in mice results in profound immunodeficiency and multi-organ lymphocytic infiltration (Dalmasso et al, 1963; Sakaguchi et al, 1982), due to defects in development of both naïve T cells and Treg cells, respectively (Sakaguchi et al, 1995). By contrast, neonatal thymectomy in humans, which is performed during cardiac surgery to repair congenital abnormalities, does not impair survival or result in deleterious consequences.…”

The Thymus and Recovery of the Sheep Erythrocyte Response in Irradiated Mice

“…A second and equally important question is whether thymus function is mediated by cells or a soluble factor, a question which has not been satisfactorily answered despite its investigation in a number of laboratories (18)(19)(20)(21)(22)(23)(24). While our studies do not settle this point, the experiments with late thymectomy and with thymus grafts help to delineate the question in several ways.…”

State of the Art: Role of the Dendritic Cell in Induction of Allograft Tolerance

“…27 Transplantation of allogeneic thymic grafts into thymectomized mice resulted in development of chimerism, co-existence of both donor- and recipient-derived blood cells, such that the animal readily accepted skin grafts from both the donor and the host. 28 More than twenty years later, the thymus was definitively identified as the site of T cell maturation and the anatomic location at which self-reactive T cells are commanded to self-destruct or are rendered anergic. 293031…”