CD8 THYMOCYTES DERIVED FROM 3,3',4,4'-TETRACHLOROBIPHENYL-EXPOSED FETAL THYMUSES POSSESS KILLING ACTIVITY

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and its congeners such as 3 ,3',4,4'-tetrachlorobiphenyl (TCB) cause immuno-suppression in experim ental animals and possibly in humans. In previous studies we found tha t exposure of murine fetal thymic organ cultures (FTOCs) to TCDD or TC B reduced the proliferative capacity of immature thymocytes, At the sa me time, the kinetics of thymocyte maturation was changed, and thymocy te differentiation was skewed toward CD4(-)CD8(+) phenotypically matur e cells. Here, we analyze the biological activities of thymocytes gene rated in TCB-exposed fetal thymus to determine whether these cells are also functionally mature. C57BL/6 fetal thymic lobes from Day 15 of g estation were explanted and grown for 8 days in FTOC in the presence o r absence of 3.3 mu M TCB, Then, the functions of total thymocytes or sorted subsets thereof were tested, We found that thymocytes from TCB- exposed lobes responded to stimulation by Con A or anti-CD3 and posses sed cytotoxic activity upon cultivation in the presence of H-2 allogen ic spleen cells. Further analysis showed that the overall cytotoxic ac tivity of thymocytes was mainly due to the CD4(-)CD8(+) cells. Our res ults suggest that the CD4(-)CD8(+) cells, which are generated in subst antially increased numbers in TCB-exposed fetal thymus, are functional ly competent cells. (C) 1995 Academic Press,lnc.