CD8 thymocytes derived from 3,3',4,4'-tetrachlorobiphenyl-exposed fetal thymi possess killing activity.

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and its congeners such as 3,3',4,4'-tetrachlorobiphenyl (TCB) cause immunosuppression in experimental animals and possibly in humans. In previous studies we found that exposure of murine fetal thymic organ cultures (FTOCs) to TCDD or TCB reduced the proliferative capacity of immature thymocytes. At the same time, the kinetics of thymocyte maturation was changed, and thymocyte differentiation was skewed toward CD4-CD8+ phenotypically mature cells. Here, we analyze the biological activities of thymocytes generated in TCB-exposed fetal thymus to determine whether these cells are also functionally mature. C57BL/6 fetal thymic lobes from Day 15 of gestation were explanted and grown for 8 days in FTOC in the presence or absence of 3.3 microM 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 possessed cytotoxic activity upon cultivation in the presence of H-2 allogenic spleen cells. Further analysis showed that the overall cytotoxic activity of thymocytes was mainly due to the CD4-CD8+ cells. Our results suggest that the CD4-CD8+ cells, which are generated in substantially increased numbers in TCB-exposed fetal thymus, are functionally competent cells.