The effects of TCDD on the activation of ovalbumin (OVA)-specific DO11.10 transgenic CD4+ T cells in adoptively transferred mice

David M. Shepherd, Erica A. Dearstyne, Nancy I. Kerkvliet

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)340-350
Number of pages11
JournalToxicological Sciences
Volume56
Issue number2
DOIs
StatePublished - 2000

Keywords

  • CD4 T cells
  • DO11.10
  • Immunotoxicity
  • In vivo
  • Mouse
  • Ovalbumin
  • TCDD
  • Transgenic

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