Reversibility of thymic atrophy induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and bis(tri-n-butyltin)oxide (TBTO).

We studied the reversibility of thymic atrophy induced by intubation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 10 days after a single dose of 50 micrograms/kg, or bis(tri-n-butyltin)oxide (TBTO), 4 days after a single dose of 75 mg/kg. This was done by an experimental design in which the atrophic thymus was placed in an in vivo situation in which the toxic chemical was no longer present, e.g. by transplantation of atrophic thymic lobes in untreated normal rats with connection to the vasculature of the recipient. At 20 days after the transplantation, the atrophic thymus showed the morphology and architecture of a normal uninvoluted thymus: lymphocyte counts and phenotypic expression of markers on lymphocytes, epithelium, and macrophages in the transplanted lobe did not differ from those in untreated donor rats or those in the normal uninvoluted thymus. Considering the mechanism of action of the toxic chemical, TBTO has been claimed to affect preferentially (passenger) lymphocytes in the thymus: the recovery after transplantation therefore is explained on the mere influx of newly-recruited precursor cells from the bone marrow. For TCDD a toxic action on the stationary epithelial component of the thymus has been claimed. We conclude that this epithelial damage is reversible within the 3-week period of the present experiment, with respect to both the morphology and immunologic phenotype of epithelium and other cell populations, as well as the recruitment of lymphocytes.