ToxSci Advance Access published online on February 22, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj142
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1 Department of Pharmacology & Therapeutics, University College Cork, Cork, Ireland; Environmental Research Institute, University College Cork, Cork, Ireland; present address: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
* To whom correspondence should be addressed. Immune-modulation by heavy metals may cause serious adverse health effects in humans although the mechanisms involved are not well understood. Both cadmium and lead are important environmental and occupational toxins. Therefore, in the current study, the co-stimulatory/adjuvant effects and T cell activating potential of these metals, (i.e. CdCl2 and PbCl2) are examined. These immune-modulating properties are critical in the development of conditions such as allergy, hypersensitivity and autoimmunity. Using the direct and reporter antigen-popliteal lymph node assay (RA-PLNA) both metals were examined individually for immunotoxicity. Mercury (i.e. HgCl2), was included for comparative purposes as its effects in the RA-PLNA are well documented. Seven days following a single footpad injection containing metal and/or reporter antigen (TNP-OVA or TNP-Ficoll), BALB/c mice were sacrificed and the PLN removed. PLN cellularity, TNP-specific antibody secreting cells (ASC) and lymphocyte subsets were assessed. All three metals strongly stimulated T and B cell proliferation and ASC production following co-injection with the reporter antigen TNP-OVA. In each case, ASC production was skewed towards the IgG1 isotype. In addition, all three metals induced IgG production to TNP-Ficoll (although relatively weakly in the case of Cd). These results show that each of these metals can provide adjuvant signals to promote lymphocyte proliferation and enhance adaptive immune responses to unrelated antigens. Skewing of immune responses towards T helper, type 2 (Th2) responses suggests that each of these metals can enhance allergic and hypersensitivity reactions to environmental antigens. Furthermore, the induction of IgG responses to TNP-Ficoll, a T cell independent antigen, indicates that each of these metals can activate neoantigen-specific T cells. T cell activation by metals can lead to metal hypersensitivity and has been implicated in the development of autoimmunity. These results are the first such accounts of immune-modulation by CdCl2 and PbCl2 in the RA-PLNA.
Received November 25, 2005
Accepted February 20, 2006
Immunotoxiocology
Immune-modulation by cadmium and lead in the acute RA-PLNA
John B Carey 1,
Ashley Allshire 2,
and
Frank N van Pelt 2 *
2 Department of Pharmacology & Therapeutics, University College Cork, Cork, Ireland; Environmental Research Institute, University College Cork, Cork, Ireland
Frank N van Pelt, E-mail: f.vanpelt{at}ucc.ie
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