B7-1 and B7-2 co-stimulatory molecules are required for mercury-induced autoimmunity

Bagenstose, Lee M.; Class, Reiner; Salgame, Padmini; Monestier, Marc

doi:10.1046/j.1365-2249.2002.01700.x

Cited by 27 publications

(21 citation statements)

References 52 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We have previously observed that in the GVHD model used here, chronic GVHD can be converted to acute GVHD by the administration of agents that promote T H 1 cytokine responses, for example, administration of recombinant interleukin 12 (Via et al 1994), or by highly selective costimulatory blockade in which the down-regulatory signal delivered by CTLA4 through its preferential ligand CD80 is inhibited (Lang et al 2002). Because both CD80 and CD86 appear to be required for HgIA (Bagenstose et al 2002), we are currently investigating whether low-dose iHg preexposure promotes T H 1 cytokine production and/or interferes with CTLA4-CD80 expression or ligand binding.…”

Section: Discussionmentioning

confidence: 96%

Low-dose exposure to inorganic mercury accelerates disease and mortality in acquired murine lupus.

Via

Nguyen

Niculescu

et al. 2003

Environ Health Perspect

View full text Add to dashboard Cite

Inorganic mercury (iHg) is known to induce autoimmune disease in susceptible rodent strains. Additionally, in inbred strains of mice prone to autoimmune disease, iHg can accelerate and exacerbate disease manifestations. Despite these well-known links between iHg and autoimmunity in animal models, no association between iHg alone and autoimmune disease in humans has been documented. However, it is possible that low-level iHg exposure can interact with disease triggers to enhance disease expression or susceptibility. To address whether exposure to iHg can alter the course of subsequent acquired autoimmune disease, we used a murine model of acquired autoimmunity, lupus-like chronic graft-versus-host disease (GVHD), in which autoimmunity is induced using normal, nonautoimmune prone donor and F1 recipient mice resistant to Hg-induced autoimmunity. Our results indicate that a 2-week exposure to low-dose iHg (20 or 200 micro g/kg every other day) to donor and host mice ending 1 week before GVHD induction can significantly worsen parameters of disease severity, resulting in premature mortality. iHg pretreatment clearly worsened chronic lupus-like disease, rather than GVHD worsening iHg immunotoxicity. These results are consistent with the hypothesis that low-level, nontoxic iHg preexposure may interact with other risk factors, genetic or acquired, to promote subsequent autoimmune disease development.

show abstract

Section: Discussionmentioning

confidence: 96%

Low-dose exposure to inorganic mercury accelerates disease and mortality in acquired murine lupus.

Via

Nguyen

Niculescu

et al. 2003

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…The role of B7 molecules in mHgIA has been examined using anti-B7-1 and anti-B7-2 Abs. Treatment with both Abs combined suppressed both short-and long-term mercury-induced hypergammaglobulinemia and ANoA (23). If mercury exposure was of brief duration anti-B7-1 Abs inhibited, while anti-B7-2 delayed ANoA production; however, these effects could be overcome by prolonged mercury exposure (23).…”

Section: Discussionmentioning

confidence: 96%

“…Significantly, exposure of lupusprone mice to low doses of mercury exacerbates idiopathic disease (21), suggesting that idiopathic lupus and mHgIA may share common pathogenic mechanisms. Analogous with idiopathic lupus mHgIA can be suppressed by anti-CD40 ligand (CD40L) Ab or CTLA-4 Ig (22), or a combination of anti-B7-1 (CD80) and anti-B7.2 (CD86) Abs (23). Individually, anti-CD86 Ab suppressed anti-nucleolar autoantibodies (ANoA) and reduced IgE but anti-CD80 Ab was only able to partially reduce the ANoA response (23).…”

mentioning

confidence: 99%

“…Analogous with idiopathic lupus mHgIA can be suppressed by anti-CD40 ligand (CD40L) Ab or CTLA-4 Ig (22), or a combination of anti-B7-1 (CD80) and anti-B7.2 (CD86) Abs (23). Individually, anti-CD86 Ab suppressed anti-nucleolar autoantibodies (ANoA) and reduced IgE but anti-CD80 Ab was only able to partially reduce the ANoA response (23). In vitro anti-CD40L, anti-CD80, and to a lesser extent anti-CD86 Ab inhibited mercury-induced T cell proliferation although none of these Abs was as effective as anti-IL-1␣ Ab (24).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Costimulation Requirements of Induced Murine Systemic Autoimmune Disease

Pollard¹,

Arnush²,

Hultman

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Costimulation between T cells and APC is required for productive immune responses. A number of receptor/ligand pairs have been shown to mediate costimulation, including CD28/B7 molecules (CD80 and CD86), CD40/CD40 ligand (CD40L, CD154), and LFA-1 (CD18)/ICAM-1 (CD54). T-B cell costimulation also plays a significant role in autoimmune diseases such as systemic lupus erythematosus. Murine HgCl2-induced autoimmunity (mHgIA) is a T cell-dependent systemic autoimmune disease that shares a number of common pathogenic mechanisms with idiopathic lupus. In this report, the significance of costimulation in mHgIA is examined by attempting to induce disease in mice deficient in either CD40L, CD28, or ICAM-1. Unlike absence of ICAM-1, homozygous deficiencies in either CD40L or CD28 significantly reduced the development of mHgIA. CD40L displayed a gene dosage effect as heterozygous mice also showed reduction of autoantibody responses and immunopathology. Markers of T cell activation such as CD44 and CTLA-4 were associated with disease expression in wild-type and ICAM-1-deficient mice but not in CD40L- or CD28-deficient mice. Absence of CTLA-4 expression in CD40L−/− mice suggests that signaling via both CD28 and CD40L is important for T cell activation and subsequent autoimmunity in mHgIA. Attempts to circumvent the absence of CD40L by increasing CD28 signaling via agonistic Ab failed to elicit CTLA-4 expression. These findings indicate that breaking of self-tolerance in mHgIA requires signaling via both the CD28/B7 and CD40/CD40L pathways.

show abstract

“…It has been shown that CD80 and CD86 can influence the immune response to immunogens by stimulating differentiation of CD4 + T cells into Th1 and Th2 lineages [23,24]. However, it remains highly controversial whether CD80 and CD86 possess distinct roles in the differentiation and regulation of Th1 and Th2 cells [25].…”

Section: Introductionmentioning

confidence: 99%

Role of CD80 and CD86 in host immune responses to the recombinant hemagglutinin domain of Porphyromonas gingivalis gingipain and in the adjuvanticity of cholera toxin B and monophosphoryl lipid A

Zhang

Lewis

Michalek

et al. 2007

Vaccine

View full text Add to dashboard Cite

The gingipains of Porphyromonas gingivalis have been implicated in the virulence of this bacterium, and antibodies to the hemagglutinin/adhesin domain (HArep) of the gingipains have been shown to protect against P. gingivalis colonization. However, the cellular mechanisms involved in host responses to HArep have not been elucidated. The purpose of the present study was to determine the functional role of CD80 and CD86 in mediating systemic and mucosal immune responses to the recombinant HArep derived from the gingipain Kgp (Kgp-HArep) after intranasal (i.n.) immunization. We also investigated the effect of the mucosal adjuvants the B subunit of cholera toxin (CTB) and monophosphoryl lipid A (MPL) on the functional role of the costimulatory molecules for the induction of systemic and mucosal responses to Kgp-HArep Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

show abstract

B7-1 and B7-2 co-stimulatory molecules are required for mercury-induced autoimmunity

Cited by 27 publications

References 52 publications

Low-dose exposure to inorganic mercury accelerates disease and mortality in acquired murine lupus.

Low-dose exposure to inorganic mercury accelerates disease and mortality in acquired murine lupus.

Costimulation Requirements of Induced Murine Systemic Autoimmune Disease

Role of CD80 and CD86 in host immune responses to the recombinant hemagglutinin domain of Porphyromonas gingivalis gingipain and in the adjuvanticity of cholera toxin B and monophosphoryl lipid A

Contact Info

Product

Resources

About