The popliteal lymph node assay in mice to screen for the immune disregulating potential of chemicals — A preliminary study

Kammüller, Michael; Thomas, Claire Le; Bakker, J.M. De; Bloksma, N.; Seinen, Willem

doi:10.1016/0192-0561(89)90167-7

Cited by 84 publications

(33 citation statements)

References 21 publications

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“…The popliteal lymph node assay (PLNA) (15)(16)(17), using TNP-OVA as bystander Ag to facilitate the read out of the responses, was shown to be extremely suitable for this purpose (10). Using this assay, we have previously shown that immunostimulating chemicals may differently dictate the type of response to the bystander Ag, TNP-OVA, and that the use of this bystander Ag facilitates the assessment of immunomodulating effects of a specific treatment in drug-induced responses (10,18).…”

Section: Differential Requirement For Cd28/ctla-4-cd80/cd86mentioning

confidence: 99%

Differential Requirement for CD28/CTLA-4-CD80/CD86 Interactions in Drug-Induced Type 1 and Type 2 Immune Responses to Trinitrophenyl-Ovalbumin

Nierkens¹,

Aalbers²,

Bol³

et al. 2005

The Journal of Immunology

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The use of mAbs to abrogate costimulatory interactions has attracted much attention with regard to prevention and modulation of adverse (auto)immune-like reactions. However, the role of costimulatory molecules and possible therapeutic use of Ab-treatment in drug-induced immunostimulation is poorly elucidated. In the present studies, we show that CD28/CTLA-4-CD80/CD86 costimulatory interactions differently regulate drug-induced type 1 and type 2 responses to an identical bystander Ag, TNP-OVA, in BALB/c mice using the reporter Ag popliteal lymph node assay. The antirheumatic drug D-Penicillamine, which may induce lupus-like side-effects, stimulated type 2 responses against TNP-OVA, characterized by the production of IL-4 and TNP-specific IgG1 and IgE. These responses were abrogated in CD80/CD86-deficient mice and in wild-type mice that were treated with anti-CD80 and anti-CD86, or CTLA-4-Ig. Anti-CTLA-4 intensively enhanced the D-Penicillamine-induced effects. In contrast, the type 1 response (IFN-γ, TNF-α, IgG2a) to TNP-OVA induced by the diabetogen streptozotocin still developed in the absence of CD80/CD86 costimulatory signaling. In addition, it was demonstrated that coadministration of anti-CD80 and anti-CD86 mAbs slightly enhanced streptozotocin-induced type 1 responses, whereas the CTLA-4-Ig fusion protein completely abrogated this response. In conclusion, different drugs may stimulate distinct types of immune responses against an identical bystander Ag, which are completely dependent on (type 2) or independent of (type 1) the CD28/CTLA-4-CD80/CD86 pathway. Importantly, the effects of treatment with anti-CD80/CD86 mAbs and CTLA-4-Ig may be considerably different in responses induced by distinct drugs.

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Section: Differential Requirement For Cd28/ctla-4-cd80/cd86mentioning

confidence: 99%

Differential Requirement for CD28/CTLA-4-CD80/CD86 Interactions in Drug-Induced Type 1 and Type 2 Immune Responses to Trinitrophenyl-Ovalbumin

Nierkens¹,

Aalbers²,

Bol³

et al. 2005

The Journal of Immunology

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“…Several new end points of potential usefulness in the assessment of chemically induced immunotoxicity have been proposed in recent years (4,6,16,17,42 (71). The popliteal lymph node (PLN) enlargment in mice and rats was proposed as a predictive test of autoimmunity-inducing drugs (31,32). While the mechanism of PLN enlargment by low-moleculer autoimmunity-inducing drugs is not well understood, results obtained with the graft-versus-host technique and quantification of activated CD4+ and CD8+ T-cell subsets by flow cytometry provided unequivocal evidence for chemical-induced dysregulation leading to autoimmune phenomena (14,31,72).…”

Section: Evaluation Of Chemicalinduced Immunotoxicitymentioning

confidence: 99%

Approaches to the Evaluation of Chemical-Induced Immunotoxicity

Krzystyniak¹,

Tryphonas²,

Fournier³

1995

Environmental Health Perspectives

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The immune system plays a crucial role in maintaining health; however, accumulating evidence indicates that this system can be the target for immunotoxic effects caused by a variety of chemicals including the environmental pollutants of polychlorinated biphenyls, chlorinated dibenzo-p-dioxins, pesticides, and heavy metals. Adverse chemical-induced immunomodulation, which is studied within the discipline of immunotoxicology, may be expressed either as immunosuppressionfimmunodepression or immunoenhancement. The former may be manifested either as decreased resistance to opportunistic viral, bacterial, fungal, and other infectious agents or increased susceptibility to cancer. Immunoenhancement on the other hand may either increase the risk of autoimmune reactions or result in allergic reactions. This paper attempts to integrate several aspects of the immune system that are relevant to the assessment of potentially immunotoxic chemicals. Environ Health Perspect 103(Suppl 9): 17-22 (1995)

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“…To date, over 60 chemicals have been tested this way and compounds known to induce adverse immune effects in man generally induced positive PLN reactions in mice as judged by an increase in PLN weight or cell count. 4,5 Among the various compounds extensively studied in the PLNA are HgCl 2 and the anticonvulsant drug diphenylhydantoin [phenytoin; DPH]. Both compounds are capable of inducing profound immune disregulation including a systemic lupus erythematosus (SLE)-like syndrome in man, and are found to cause T-cell-dependent lymphoproliferative responses and antibody production in the PLNA in mice.…”

Section: Introductionmentioning

confidence: 99%

The autoimmunogenic chemicals HgCl₂ and diphenylhydantoin stimulate IgG production to TNP–Ficoll and TNP–OVA, supporting and extending the graft‐versus‐host hypothesis for chemical induction of autoimmunity

et al. 1996

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SUMMARYBypass of T-cell tolerance via non-cognate graft-versus-host (GVH)-like help from T-helper (Th) cells activated by chemically altered or induced epitopes, has been postulated as a mechanism underlying chemical induction of autoimmunity. To functionally test this hypothesis, we assessed whether the autoimmunogenic chemicals HgCl 2 and diphenylhydantoin (DPH), like GVH reactions, stimulate specific immunoglobulin G (IgG) responses to trinitrophenyl (TNP)-Ficoll but not to TNP-ovalbumin. IgG responses were quantified in the popliteal lymph node by enzyme-linked immunosorbent spotforming cell assay (ELISPOT) assays 7 days after s.c. injection of antigens, parental cells, chemicals or combinations thereof into the footpad of semi-allogeneic F1 mice. Antigens, chemicals, or cells alone induced few TNP-specific IgG antibody-forming cell (AFC) compared with untreated mice. Coinjection of parental cells or chemicals with TNP-Ficoll stimulated the TNP-specific response per lymph node 50-and 40-fold, respectively. In contrast, the IgG response to TNP-ovalbumin could not be stimulated by GVH reactions, whereas HgCl 2 and DPH dose-dependently increased this response up to 25-and 250-fold, respectively. However, responses to TNP-ovalbumin pre-incubated with HgCl 2 or DPH could be stimulated 6-8 fold by GVH reactions. Observed similar adjuvanticity of chemicals and parental cells for TNP-Ficoll support a GVH-like action of autoimmunogenic chemicals. In addition, the chemicals modify TNP-ovalbumin such that B cells recognizing this antigen become susceptible to noncognate stimulation by GVH reactions.

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The popliteal lymph node assay in mice to screen for the immune disregulating potential of chemicals — A preliminary study

Cited by 84 publications

References 21 publications

Differential Requirement for CD28/CTLA-4-CD80/CD86 Interactions in Drug-Induced Type 1 and Type 2 Immune Responses to Trinitrophenyl-Ovalbumin

Differential Requirement for CD28/CTLA-4-CD80/CD86 Interactions in Drug-Induced Type 1 and Type 2 Immune Responses to Trinitrophenyl-Ovalbumin

Approaches to the Evaluation of Chemical-Induced Immunotoxicity

The autoimmunogenic chemicals HgCl₂ and diphenylhydantoin stimulate IgG production to TNP–Ficoll and TNP–OVA, supporting and extending the graft‐versus‐host hypothesis for chemical induction of autoimmunity

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The popliteal lymph node assay in mice to screen for the immune disregulating potential of chemicals — A preliminary study

Cited by 84 publications

References 21 publications

Differential Requirement for CD28/CTLA-4-CD80/CD86 Interactions in Drug-Induced Type 1 and Type 2 Immune Responses to Trinitrophenyl-Ovalbumin

Differential Requirement for CD28/CTLA-4-CD80/CD86 Interactions in Drug-Induced Type 1 and Type 2 Immune Responses to Trinitrophenyl-Ovalbumin

Approaches to the Evaluation of Chemical-Induced Immunotoxicity

The autoimmunogenic chemicals HgCl2 and diphenylhydantoin stimulate IgG production to TNP–Ficoll and TNP–OVA, supporting and extending the graft‐versus‐host hypothesis for chemical induction of autoimmunity

Contact Info

Product

Resources

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The autoimmunogenic chemicals HgCl₂ and diphenylhydantoin stimulate IgG production to TNP–Ficoll and TNP–OVA, supporting and extending the graft‐versus‐host hypothesis for chemical induction of autoimmunity