Development of multiple organ-localized autoimmune diseases in nude mice after reconstitution of T cell function by rat fetal thymus graft.

Abstract

The T cell function of congenitally athymic nude mice and rats, as well as the severe immunodeficiency resulting from thymic dysplasia in humans, can be corrected by implantation of intact thymus or thymic epithelium (1-5). Either syngeneic or allogeneic thymic grafts are effective for reconstituting T cell functions in congenitally thymus-deficient rodents (6-10), although these functions are generally less effective than those of intact normal animals. Such reconstituted nude mice (grafted with allogeneic thymus or thymic epithelial cells) accept skin grafts from the syngeneic and the donor strain, whereas those derived from a third strain are vigorously rejected (4, 1 1).In the present experiments, attempts were made to reconstitute T cell functions of nude mice by transplantation of thymic rudiments obtained from embryonic rats. The results show that these grafted mice gained T cell-mediated immune function, and accepted skin grafts from the donor rat strain. These mice, however, developed severe multiple organ-localized autoimmune diseases showing features similar to the autoimmunity observed in the mice after neonatal thymectomy, as reported previously (12-16). Materials and MethodsThymic Rudiment Transplantation. The rudiments of the thymuses were aseptically dissected from 15-d-old F344/DuCcj (F344) or ACI/NMs (ACI) rat embryos or 14-d-old BALB/cAJcl (BALB/c) mouse embryos (observation of vaginal plug = day 0). Female BALB/~ nu/nu mice, 5 wk of age, (Clea Japan Inc., Tokyo, Japan) were grafted under each kidney subcapsule with two lobes of thymic rudiments. This was done with an orally controlled micropipette introduced through a dorsal incision exposing the kidney. All mice were housed in a conventional animal-care facility.Chromosome Analysis. Chromosome analysis of lymphoid cells of thymic grafts was carried out by the air-drying method (17). The cells were harvested from 5 BALB/c nu/nu mice 8 wk after grafting with F344 thymic rudiments. Colchicine (0.05 mg/g body weight) was injected subcutaneously 2 h before harvest. Cells were treated with 1% sodium citrate in water for 5 rain at 37°C, fixed in cold acetic acid/methanol (1:1), and then

L3T4 effector cells in multiple organ-localized autoimmune disease in nude mice grafted with embryonic rat thymus.

“…The previous study (1) showed the development ofmultiple organ-localized autoimmune disease in TG nude mice. To characterize the effector cells in these autoimmune diseases, passive transfer of the lesions was attempted .…”

“…Female BALB/c nu/nu mice, 5 wk of age, (CleaJapan Inc.) were grafted under each kidney subcapsule with two lobes ofthymic rudiments . These TG nude mice developed multiple organ-localized autoimmune diseases as reported previously (1). Incidence of the diseases assessed by histological examination in 109 TG nude mice, which were used as donors for the transfer experiments, was as follows : ovary, 92%; thyroid gland, 72 %; stomach, 72% ; adrenal gland, 44% ; salivary gland, 98%.…”

“…Considerable antibody responses to SRBC antigen were also observed. Histological and immunological studies, however, showed severe development ofmultiple organ-localized autoimmune diseases, especially in endocrine organs such as thyroid and ovary (1).…”

“…The basis of this function is dependent on interactions between the T cell precursors and nonlymphoid components, such as thymic epithelial cells. Recently we demonstrated that the T cell function of congenitally athymic nude (nu/nu) mice can be corrected by implantation of xenogeneic thymic rudiments from embryonic rat (1) . Namely, rat thymic rudiments transplanted under renal subcapsule of nude mice developed well and formed a proper thymic structure composed ofdonor epithelia and host lymphocytes .…”

Allogeneic Neonatal Neuronal Retina Grafts Display Partial Immune Privilege in the Subcapsular Space of the Kidney

“…The destruction of allogeneic NNR grafts in this circumstance, compared with similar syngeneic NNR grafts, indicates that NNR as a tissue is only partially immune-privileged. As mentioned previously, allogeneic grafts of testis (16,20), neonatal retinal pigment epithelium (10), and epithelium-deprived corneas (14) survive almost indefinitely beneath the kidney capsule, which is characteristic of tissues that express complete immune privilege. In the case of testis, neonatal retinal pigment epithelium, and epithelium-deprived cornea grafts, constitutive expression of CD95 ligand (CD95L) has been implicated in conferring on these tissues the immune-privileged status (10,14,16).…”