Abstract
Although exposure to 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) clearly impairs T cell-dependent immune responses, the mechanisms underlying TCDD-induced T cell dysfunction are unclear. With the goal of determining precisely how exposure to TCDD impairs the activation of CD8 + T cells in vivo, we used a well-defined T cell receptor (TCR) transgenic system. Greater than 95% of the CD8 + T cells in F5 transgenic mice possess TCR specific for a peptide from influenza A virus expressed in the context of H-2D b. Unexpectedly, we discovered that exposure to TCDD did not alter CD8 + T cell function in the transgenic mice. Specifically, treatment of F5 mice with TCDD did not affect the recruitment of virus-specific CD8 + T cells to the lung, nor did it impair the ability of CD8 + T cells in the lymph node to produce cytokines, or to clonally expand or differentiate. This is in direct contrast to the suppressive effects of TCDD on the response of CD8 + T cells in wild-type mice. Exposure of F5 mice to TCDD induced CYP1A1 and suppressed the production of virus-specific antibodies. Likewise, upon adoptive transfer into wild-type mice, TCDD suppressed the expansion and differentiation of F5-derived CD8 + T cells. This indicates that the F5 mice and lymphocytes derived from them are not inherently resistant to the immunosuppressive effects of TCDD. Rather, our data suggest that in the context of a supraphysiological number of antigen-specific CD8 + T cells, the function of these cells was not affected by exposure to TCDD. Given that antibody production in the F5 mice was sensitive to suppression by TCDD, while the CD8 response was resistant, our data provide a new perspective on the ways in which exposure to TCDD adversely affects B and T lymphocyte function.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.