Th1/Th2 cytokine gene expression after mercuric chloride in susceptible and resistant rat strains

Gillespie, Kathleen M.; Saoudi, Abdelhadi; Kühn, J.; Whittle, Catheryne; Druet, Philippe; Bellon, B; Mathieson, Peter W.

doi:10.1002/eji.1830261018

Cited by 63 publications

(78 citation statements)

References 30 publications

(27 reference statements)

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“…The disease has been frequently studied as a model for drug-induced autoimmunity in humans [24]. HgCl 2 preferentially activates Th2 cells in the BN rat, resulting in high production of IL-4 and IgE [25,26]. We observed an early increase of CD134 expression in this model in a specific subset of CD4 ϩ T lymphocytes, the CD45RC lo cells [21].…”

Section: Introductionmentioning

confidence: 70%

“…Because HgCl 2 -induced autoimmunity is characterized by activation of Th2 cells and high production of IL-4 [26], the role of IL-4 in regulation of CD134 expression was examined. As depicted in Figure 4, addition of culture supernatant from CHO cells producing recombinant rat IL-4 to an LN cell culture could dose-dependently increase the number of CD134-expressing cells until a maximum of about 30% of the CD4 ϩ cell population (Fig.…”

Section: The Role Of Il-4 In Induction Of Cd134 Expressionmentioning

confidence: 99%

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Strong expression of CD134 (OX40), a member of the TNF receptor family, in a T helper 2-type cytokine environment

Roos

Schilder-Tol

Weening

et al. 1998

Journal of Leukocyte Biology

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Section: Introductionmentioning

confidence: 70%

Section: The Role Of Il-4 In Induction Of Cd134 Expressionmentioning

confidence: 99%

Strong expression of CD134 (OX40), a member of the TNF receptor family, in a T helper 2-type cytokine environment

Roos

Schilder-Tol

Weening

et al. 1998

Journal of Leukocyte Biology

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“…ϩ Th2 cells (10) and is associated with increased production of IL-4 and IL-10 and early marginal increases in IL-2 and IFN-␥ (11). Polyclonal activation of B cells results in hypergammaglobulinemia of the Th2-related IgG1 and IgE isotypes (7).…”

Section: F Ollowing Activation Naive Cd8mentioning

confidence: 99%

Regulatory CD8+ T Cells Control Neonatal Tolerance to a Th2-Mediated Autoimmunity

Field

Caccavelli

Bloch

et al. 2003

The Journal of Immunology

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Exposure of newborn animals to a foreign Ag may result in immunological tolerance to that specific Ag, a phenomenon called neonatal tolerance. We have previously reported that neonatal administration to Brown-Norway rats of mercury, a heavy metal toxicant, induces a dominant tolerance, specific for the chemical otherwise responsible for Th2 cell-mediated autoimmune responses in this susceptible strain of rats. Neonatal exposure to Ags can prime immunity, rather than inactivate or delete responses, and sustain regulatory functions effective against autoreactive T cells. Here, we address whether such a tolerant response is due to the generation of regulatory cells. The results suggest that the CD8+ T cell subset is involved in neonatal tolerance to mercuric salt-induced Th2 autoimmune disease. Thus, we demonstrate that in vivo CD8 depletion breaks tolerance following mercury recall in animals under a neonatal tolerance protocol. Furthermore, adoptive cotransfer of splenocytes from naive and tolerant rats as well as transfer of CD8+ T cells from tolerant animals prevent naive syngeneic rats from developing pathologic Th2 immune responses. These observations indicate that CD8+ T cells are endowed with regulatory functions in neonatal tolerance and mediate active suppression. Moreover, neonatal tolerance induced the expansion of CD8+CD45RChigh T cells and the emergence of a high percentage of IFN-γ-synthesizing CD8+ T cells, which probably reflects the implication of regulatory Tc1 cells. Thus, in vivo induction of neonatal tolerance suppresses Th2 autoimmune responses via generation of a CD8+ cell-mediated regulatory response.

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“…In contrast, IL-4 biases T cells toward a Th2 phenotype (23 (29) as well as slight increases in IL-12 mRNA levels in spleen and lymph nodes from these animals (30). In these studies, HgCl2 failed to induce increases of cytokines in resistant LEW rats (29,30). mRNA analysis revealed higher baseline levels of IFN-y (29) and (30) (35).…”

Section: Description Of the Modelmentioning

confidence: 96%

Cytokine Regulation of a Rodent Model of Mercuric Chloride-Induced Autoimmunity

Bagenstose¹,

Salgame²,

Monestier³

1999

Environmental Health Perspectives

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Experimental models of chemically induced autoimmunity have contributed to our understanding of the development of autoimmune diseases in humans. Heavy metals such as mercury induce a dramatic activation of the immune system and autoantibody production in genetically susceptible rats and mice. This autoimmune syndrome is dependent on T cells, which are important for B-Cell activation and cytokine secretion. Several studies have focused on the roles of T-helper (Th)1 and Th2 cells and their respective cytokines in the pathogenesis of mercury-induced disease. This article reviews recent studies that have examined the patterns of cytokine gene expression and where investigators have manipulated the Thl and Th2 responses that occur during mercury-induced autoimmunity. Finally, we will discuss some biochemical/molecular mechanisms by which heavy metals may induce cytokine gene expression.

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Th1/Th2 cytokine gene expression after mercuric chloride in susceptible and resistant rat strains

Cited by 63 publications

References 30 publications

Strong expression of CD134 (OX40), a member of the TNF receptor family, in a T helper 2-type cytokine environment

Strong expression of CD134 (OX40), a member of the TNF receptor family, in a T helper 2-type cytokine environment

Regulatory CD8+ T Cells Control Neonatal Tolerance to a Th2-Mediated Autoimmunity

Cytokine Regulation of a Rodent Model of Mercuric Chloride-Induced Autoimmunity

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