TI:

Title
Immune Modulation by Cadmium and Lead in the Acute Reporter Antigen-Popliteal Lymph Node Assay

AU:

Author
Carey, John B; Allshire, Ashley; van Pelt, Frank N

AF:

Author Affiliation
Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland

SO:

Source
Toxicological Sciences [Toxicol. Sci.]. Vol. 91, no. 1, pp. 113-122. May 2006.

IS:

ISSN
1096-6080

DE:

Descriptors
Metals; Hypersensitivity; Lymphocytes T; Lymph nodes; Immunoglobulin G; Lead; Adjuvants; Cadmium; Autoimmunity; Immunotoxicity; Toxins; Mercury; Lymphocytes B; Immunomodulation; Heavy metals

AB:

Abstract
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 costimulatory/adjuvant effects and the T-cell-activating potential of these metals (i.e., CdCl sub(2) and PbCl sub(2)), are examined. These immune-modulating properties are critical in the development of conditions such as allergy, hypersensitivity, and autoimmunity. Using the direct popliteal lymph node assay (PLNA) and reporter antigen-popliteal lymph node assay (RA-PLNA) both metals were examined individually for immunotoxicity. Mercury (i.e., HgCl sub(2)) 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 RA (trinitrophenyl-ovalbumin [TNP-OVA] or TNP-Ficoll), BALB/c mice were sacrificed and the popliteal lymph nodes (PLNs) removed. PLN cellularity, TNP-specific antibody-secreting cells (ASCs), and lymphocyte subsets were assessed. All three metals strongly stimulated T- and B-cell proliferation and ASC production following coinjection with the RA TNP-OVA. In each case, ASC production was skewed towards the IgG sub(1) 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 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. This is the first report of immune modulation by CdCl sub(2) and PbCl sub(2) in the RA-PLNA.

LA:

Language
English

SL:

Summary Language
English

PY:

Publication Year
2006

PD:

Publication Date
200605

PT:

Publication Type
Journal Article

PB:

Publisher
Oxford University Press, Oxford Journals, Great Clarendon Street Oxford OX2 6DP UK, jnl.samples@oup.co.uk, http://www3.oup.co.uk/jnls/

CL:

Classification
X 24222 Analytical procedures

UD:

Update
200604

SF:

Subfile
Toxicology Abstracts

AN:

Accession Number
6753274

PG:

Journal Pages
113-122

JV:

Journal Volume
91

JI:

Journal Issue
1