PROLIFERATION INHIBITION AND CD4 CD8 THYMOCYTE SUBSET SKEWING BY IN-VIVO EXPOSURE OF C57BL/6 MICE TO AH RECEPTOR-BINDING 3,3',4,4'-TETRACHLOROBIPHENYL/

3,3',4, 4'-Tetrachlorobiphenyl (TCB) and other Ah receptor-binding xen obiotics lead to thymus atrophy and immunosuppression, the former poss ibly causing the latter. In order to better understand the TCB-induced events in the murine thymus, we analyzed the effects of TCB on the pr oliferation capacity and maturation kinetics of different thymocyte su bsets in 2-week-old C57BL/6 mice (i.e. of the Ah(b-1) 'dioxin-sensitiv e' genotype). Mice were injected with a single dose of TCB, and the de velopment of thymocytes was followed up for 10 days using flow cytomet ric surface marker analysis combined with measurement of DNA content b y 7-amino-actinomycin D staining. Already 2 days after exposure to TCB , fewer of the more immature thymocytes (CD4-CD8-, CD4-CD8+alpha beta TCR-) were proliferating than in thymi from control animals. Eventuall y this led to a severe decrease in thymus cellularity. Moreover, a shi ft towards the CD4-CD8+ mature subpopulation was observed. The effects were reversible, and proliferation and CD4/CD8 subset distribution re turned to normal levels within the observation period. The results are in good agreement with the data obtained previously in vitro with fet al thymus organ cultures.