Induction of autoimmunity through bystander effects. Lessons
from immunological disorders induced by heavy metals.
Fournie GJ, Mas M, Cautain B, Savignac M, Subra JF, Pelletier L, Saoudi A,
Lagrange D, Calise M, Druet P.
Institut National de la Sante et de la Recherche Medicale (INSERM) U28, Institut
Federatif de Recherche (IFR) 30, Hopital Purpan and Universite Paul Sabatier,
Toulouse, France. gfournie@purpan.inserm.fr
Autoreactive T cells exist in healthy individuals and represent a potential
reservoir of pathogenic effectors which, when stimulated by microbial adjuvants,
could trigger an autoimmune disease. Experimental studies have indicated that
xenobiotics, well defined from a chemical point of view, could promote the
differentiation of autoreactive T cells towards a pathogenic pathway. It is
therefore theoretically possible that compounds present in vaccines such as
thiomersal or aluminium hydroxyde can trigger autoimmune reactions through
bystander effects.Mercury and gold in rodents can induce immunological disorders
with autoimmune reactions. In vitro, both activate signal transduction pathways
that result in the expression of cytokines, particularly of IL-4 and IFNgamma.
In a suitable microenvironment heavy metals could therefore favour the
activation of autoreactive T cells. In that respect, genetic background is of
major importance. Genome-wide searches in the rat have shown that overlapping
chromosomal regions control the immunological disorders induced by gold salt
treatment, the development of experimental autoimmune encephalomyelitis and the
CD45RC(high)/CD45RC(low)CD4(+)T cells balance. The identification and functional
characterization of genes controlling these phenotypes may shed light on key
regulatory mechanisms of immune responses. This should help to improve efficacy
and safety of vaccines. Copyright 2001 Academic Press.
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