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The Effects of TCDD on the Activation of Ovalbumin (OVA)-Specific DO11.10 Transgenic CD4+ T cells in Adoptively Transferred Mice.
- Source :
- Toxicological Sciences; Aug2000, Vol. 56 Issue 2, p340-350, 11p, 1 Diagram, 3 Charts, 3 Graphs
- Publication Year :
- 2000
-
Abstract
- Exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses the generation of T cell-dependent immunity, both humoral and cell-mediated. However, the mechanism of TCDD-induced immune suppression remains to be defined. We hypothesized that exposure to TCDD suppresses the activation of naive CD4+ T cells and prevents their expansion and differentiation into effector T-helper cells capable of driving T cell-dependent immune responses. To test this hypothesis, we adoptively-transferred DO11.10 OVA-specific T-cell receptor (TCR) transgenic T cells into syngeneic recipients and used a TCR-specific monoclonal antibody to track the in vivo activation of naive CD4+ T lymphocytes following exposure to OVA. The production of OVA-specific antibodies was suppressed in a dose-dependent manner in adoptively transferred mice that had been exposed to TCDD. Although TCDD exposure had little effect on the expansion or activation of the adoptively transferred, OVA-specific CD4+ T cells, these cells disappeared from the spleen more rapidly in TCDD-treated mice and produced significantly decreased levels of the T cell-derived cytokines IL-2 and IL-10. There was also a trend towards reduced IFN-γ and IL-4 production following in vitro re-stimulation. These data suggest that TCDD may interfere with the survival and/or differentiation of OVA-specific T-helper cells. These results demonstrate for the first time the potential of the DO11.10 adoptive transfer system to directly assess immunotoxic effects of xenobiotics on antigen-specific CD4+ T cells in vivo. [ABSTRACT FROM PUBLISHER]
- Subjects :
- TETRACHLORODIBENZODIOXIN
POLLUTANTS
T cells
IMMUNOTOXICOLOGY
TRANSGENIC mice
Subjects
Details
- Language :
- English
- ISSN :
- 10966080
- Volume :
- 56
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Toxicological Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 44405994
- Full Text :
- https://doi.org/10.1093/toxsci/56.2.340