Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 212, Issue 2, Pages 119-126Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2005.07.012
Keywords
diethylstilbestrol; T-cell selection; apoptosis; developmental toxicity
Categories
Funding
- NHLBI NIH HHS [R01 HL 058641] Funding Source: Medline
- NIAID NIH HHS [R01 AI 053703] Funding Source: Medline
- NIDA NIH HHS [R01DA016545] Funding Source: Medline
- NIEHS NIH HHS [R01ES09098] Funding Source: Medline
Ask authors/readers for more resources
Prenatal exposure to diethylstilbestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the Current study, we investigated the effects of DES oil T-cell differentiation in the thymus using the HY-TCR transgenic (Tg) mouse model in which the female mice exhibit positive selection of T cells bearing the Tg TCR, while the male mice show negative selection of such T cells. In female HY-TCR-Tg mice, exposure to DES showed more pronounced decrease in thymic cellularity when compared to male mice. Additionally, female mice also showed a significant decrease in the proportion of double-positive (DP) T cells in the thymus and HY-TCR-specific CD8(+) T cells in the periphery. Male mice exhibiting negative selection also showed decreased thymic cellularity following DES exposure. Moreover, the male mice showed increased proportion of double-negative (DN) T cells in the thymus and decreased proportion of CD8(+) T cells. The density of expression of HY-TCR oil CD8(+) cells was increased following DES exposure ill both females and males. Finally, the proliferative response of thymocytes to mitogens and peripheral lymph node T cells to male H-Y antigen was significantly altered in female and male mice following DES treatment. Taken together, these data suggest that DES alters T-cell differentiation in the thymus by interfering with positive and negative selection processes, which in turn modulates the T-cell repertoire in the periphery. (c) 2005 Elsevier Inc All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available