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Diethylstilbestrol alters positive and negative selection of T cells in the thymus and modulates T-cell repertoire in the periphery.
Toxicol Appl Pharmacol. 2006 Apr 15; 212(2):119-26.TA

Abstract

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 on 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 on CD8+ cells was increased following DES exposure in 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.

Authors+Show Affiliations

Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16122773

Citation

Brown, Nicole, et al. "Diethylstilbestrol Alters Positive and Negative Selection of T Cells in the Thymus and Modulates T-cell Repertoire in the Periphery." Toxicology and Applied Pharmacology, vol. 212, no. 2, 2006, pp. 119-26.
Brown N, Nagarkatti M, Nagarkatti PS. Diethylstilbestrol alters positive and negative selection of T cells in the thymus and modulates T-cell repertoire in the periphery. Toxicol Appl Pharmacol. 2006;212(2):119-26.
Brown, N., Nagarkatti, M., & Nagarkatti, P. S. (2006). Diethylstilbestrol alters positive and negative selection of T cells in the thymus and modulates T-cell repertoire in the periphery. Toxicology and Applied Pharmacology, 212(2), 119-26.
Brown N, Nagarkatti M, Nagarkatti PS. Diethylstilbestrol Alters Positive and Negative Selection of T Cells in the Thymus and Modulates T-cell Repertoire in the Periphery. Toxicol Appl Pharmacol. 2006 Apr 15;212(2):119-26. PubMed PMID: 16122773.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diethylstilbestrol alters positive and negative selection of T cells in the thymus and modulates T-cell repertoire in the periphery. AU - Brown,Nicole, AU - Nagarkatti,Mitzi, AU - Nagarkatti,Prakash S, Y1 - 2005/08/24/ PY - 2005/05/27/received PY - 2005/07/15/revised PY - 2005/07/18/accepted PY - 2005/8/27/pubmed PY - 2006/5/26/medline PY - 2005/8/27/entrez SP - 119 EP - 26 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 212 IS - 2 N2 - 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 on 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 on CD8+ cells was increased following DES exposure in 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. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/16122773/Diethylstilbestrol_alters_positive_and_negative_selection_of_T_cells_in_the_thymus_and_modulates_T_cell_repertoire_in_the_periphery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(05)00424-2 DB - PRIME DP - Unbound Medicine ER -