Assessment of autoimmunogenic potential of xenobiotics using the popliteal lymph node assay.
This article reviews the ability of the simple popliteal lymph node assay (PLNA) and variations thereof to assess the immunostimulating potential of low-molecular-weight xenobiotics, including pharmaceuticals. In essence, all variations of the PLNA detect the immune reaction in the popliteal lymph node to subcutaneous injection of a chemical into the footpad. The primary PLNA, in which the enlargement of popliteal lymph node is measured on injection of the chemical as such, can be regarded as a fast, simple, and reliable assay to detect and grade the immunostimulating potential of chemicals in a preclinical production phase. To prove T-cell sensitization, i.e., the involvement of T cells and/or induction of T-cell memory, secondary PLNAs or the so-called modified PLNA can be used. Secondary PLNAs can be performed in previously sensitized animals or by using adoptive T-cell transfer techniques. In the modified PLNA the well-defined reporter antigens TNP-ovalbumin and TNP-Ficoll are injected together with the chemicals and the number and isotype of the antibody-forming cells in the draining lymph node are analyzed. This modification of the PLNA enables definition of the involvement of T cells as well as type of immune response (T-cell sensitization vs mere inflammation as well as Th1 vs Th2) elicited by the chemical in an easy manner. To date, more than 100 chemicals have been tested in the PLNA and results indicate that all chemicals with documented adverse autoimmune or allergic effects in humans induce a positive PLN response. No false negatives have been found if metabolism is taken into consideration. It is important to realize that immunostimulation measured in the PLNA is only a first indication that a chemical can induce or exacerbate autoimmune(-like) disease.
Pieters
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RITOX-Immunotoxicology, Utrecht University, Utrecht, The Netherlands. R.Pieters@ritox.vet.uu.nl
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D000276:Adjuvants, Immunologic / Q000633:toxicity; D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007156:Immunologic Memory; D007158:Immunologic Techniques; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D051381:Rats; D015398:Signal Transduction; D015262:Xenobiotics / Q000276:immunology* / Q000633:toxicity*
D000276:Adjuvants, Immunologic; D015262:Xenobiotics