T cell dysfunction in the diabetes-prone BB rat. A role for thymic migrants that are not T cell precursors

Journal Article · Fri Jan 01 00:00:00 EST 1988 · J. Exp. Med.; (United States)

DOI:https://doi.org/10.1084/jem.167.1.132· OSTI ID:5592109

Georgiou, H M; Lagarde, A C; Bellgrau, D

Diabetes-prone BB (BB-DP) rats express several T cell dysfunctions which include poor proliferative and cytotoxic responses to alloantigen. The goal of this study was to determine the origin of these T cell dysfunctions. When BB-DP rats were thymectomized, T cell depleted, and transplanted with neonatal thymus tissue from diabetes-resistant and otherwise normal DA/BB F1 rats, the early restoration of T cell function proceeded normally on a cell-for-cell basis; i.e., peripheral T cells functioned like those from the thymus donor. Because the thymus in these experiments was subjected to gamma irradiation before transplantation and there was no evidence of F1 chimerism in the transplanted BB-DP rats, it appeared that the BB-DP T cell precursors could mature into normally functioning T cells if the maturation process occurred in a normal thymus. If the F1 thymus tissue was treated with dGua before transplantation, the T cells of these animals functioned poorly like those from untreated BB-DP rats. dGua poisons bone marrow-derived cells, including gamma radiation-resistant cells of the macrophage/dendritic cell lineages, while sparing the thymic epithelium. Therefore, the reversal of the T cell dysfunction depends on the presence in the F1 thymus of gamma radiation-resistant, dGua-sensitive F1 cells. Conversely, thymectomized and T cell-depleted F1 rats expressed T cell dysfunction when transplanted with gamma-irradiated BB thymus grafts. T cell responses were normal in animals transplanted with dGua-treated BB thymus grafts. With increasing time after thymus transplantation, T cells from all animals gradually expressed the functional phenotype of the bone marrow donor. Taken together these results suggest that BB-DP bone marrow-derived cells that are not T cell precursors influence the maturation environment in the thymus of otherwise normal BB-DP T cell precursors.

• Research Organization: Univ. of Colorado Health Sciences Center, Denver
• OSTI ID: 5592109
• Journal Information: J. Exp. Med.; (United States), Vol. 167:1
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
LYMPHOCYTES
BIOLOGICAL FUNCTIONS
CELL PROLIFERATION
THYMUS
IRRADIATION
TRANSPLANTS
BONE MARROW
DIABETES MELLITUS
GAMMA RADIATION
IMMUNE REACTIONS
INHIBITION
RADIATION CHIMERAS
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ANIMALS
BIOLOGICAL MATERIALS
BLOOD
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CHIMERAS
CONNECTIVE TISSUE CELLS
DISEASES
ELECTROMAGNETIC RADIATION
ENDOCRINE DISEASES
FUNCTIONS
HEMATOPOIETIC SYSTEM
IONIZING RADIATIONS
LEUKOCYTES
LYMPHATIC SYSTEM
MAMMALS
MATERIALS
METABOLIC DISEASES
MOSAICISM
ORGANS
RADIATIONS
RODENTS
SOMATIC CELLS
TISSUES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals