EVIDENCE FOR THE PROMOTION OF POSITIVE SELECTION OF THYMOCYTES BY AH RECEPTOR AGONIST 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ligand for the arylhyd rocarbon receptor (Ah receptor), abundant in the murine thymus. In the thymus immunocompetent T cells develop. Upon exposure of murine fetal thymi in organ cultures to TCDD the distribution of mature and immatu re thymocytes is skewed towards apparently mature, prospective cytotox ic cells of the CD4(-)CD8(+)T cell receptor(+) phenotype. The normally abundant CD4(+)CD8(+) cells are decreased. Proliferation of the most immature thymocyte subpopulations is inhibited and maturation of thymo cytes appears accelerated by TCDD. Eventually the thymocyte number is significantly decreased. Selective treatment of stroma cells showed th em to be the primary target cells of TCDD action. Thymus stroma plays a pivotal role in thymocyte maturation and is indispensable for the se lection of thymocytes bearing T cell receptors specific for foreign an tigen in the context of self. We tested whether the effects of TCDD on thymocyte differentiation and maturation has further consequences for the selection processes by analysing (a) the repertoire of V-beta gen es used as a measure for negative selection and (b) the expression of CD69 and bcl-2 by thymocytes as a parameter for positive selection. Ou r data indicate that TCDD does not cause gross disturbance of negative selection but provide evidence for more cells auditioning for positiv e selection by TCDD exposure.