The popliteal lymph node assay in predictive testing for autoimmunity.
A large number of chemicals or metabolites thereof is known to induce or exacerbate autoimmune disease (AID) in man. Due to the complex immunological processes involved, chemical-induced autoimmunity is hardly if ever detected in standard toxicity testing and generally applicable animal models that detect a chemical's potential to induce AID do not exist. The popliteal lymph node assay (PLNA) focusses on the chemical's ability to initiate an immune response rather than on inducing or exacerbating autoimmune reactions, and is regarded a suitable test for pre-screening of immunostimulating and -sensitizing potential. The most simple primary PLNA measures enlargement of the popliteal lymph node (PLN) 6-8 days after subcutaneous injection of a chemical into the footpad distinguishes between immunostimulating and innocent chemicals. The primary PLNA is however unable to assess the involvement of T cells and thus the immunosensitizing potential of a chemical. For this, the secondary and/or modified PLNA is appropriate. The secondary PLNA detects challenge reactions in the PLN to non-sensitizing doses of a chemical in pre-sensitized animals or in unsensitized animals that received an adoptive transfer of pre-sensitized syngeneic T cells. The modified PLNA uses the defined reporter antigens TNP-OVA (T cell-dependent antigen) and TNP-Ficoll (T cell-independent antigen) to distinguish sensitizing from non-sensitizing (IgG1-response or not to TNP-Ficoll) and mere inflammatory from complete innocent (IgG1-response or not to TNP-OVA) chemicals. To date, about 130 compounds (drugs and environmental pollutants) have been tested in either one or more of these PLNAs. Results show a good correlation with documented immunostimulating (both autoimmunogenic and allergic) potential and no false negative chemicals were detected if metabolism was considered. In particular the modified PLNA awaits validation before it can be recommended as a standard test for autoimmunogenic potential.
Pieters
R
R
Research Institute of Toxicology (RITOX)-Immunotoxicology, Utrecht University, 3508 TD, Utrecht, The Netherlands. r.pieters@ritox.vet.uu.nl
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D015551:Autoimmunity / Q000187:drug effects*; D001681:Biological Assay; D008198:Lymph Nodes / Q000187:drug effects*; D011237:Predictive Value of Tests