Popliteal lymph node assay

Aida, T. et al., Evaluation of allergenic potential of low-molecular compounds by mouse popliteal lymph node assay. J. Toxicol. Sci., 23, 425, 1998. 

Bloksma, N. et al., Predictive immunotoxicological test systems Suitability of the popliteal lymph node assay in mice and rats. Crit. Rev. Toxicol., 25, 369, 1995. 

Goebel, C. et al., The popliteal lymph node assay in mice Screening of drugs and other chemicals for immunotoxic hazard. Inflamm. Res., 45 Suppl. 2, S85,1996. 

Descotes, J., The popliteal lymph node assay A tool for studying the mechanisms of drug-induced autoimmune disorders. Toxicol. Lett., 64-65 Spec No, 101,1992. 

Albers, R. et al., The use of reporter antigens in the popliteal lymph node assay to assess immunomodulation by chemicals. Toxicol. Appl. Pharmacol., 143, 102, 1997. 

Gutting, B.W. et al., A comparison of the direct and reporter antigen popliteal lymph node assay for the detection of immunomodulation by low molecular weight compounds. Toxicol. Sci., 51, 71, 1999. 

Pieters, R., and Albers, R., Assessment of autoimmunogenic potential of xenobiotics using the popliteal lymph node assay. Methods, 19, 71, 1999. 

There are no established assays that reliably assess potential for autoimmunity and acute systemic hypersensitivity. The popliteal lymph node assay (PLNA) has only a relatively small database available for assessing its usefulness for drug regulatory purposes. 

Pieters, R. (2001). The popliteal lymph node assay a tool for predicting drug allergies. Toxicology 158 65-69. 

Ravel, G. and Descotes, J. (2005) Popliteal lymph node assay facts and perspectives./oumoi of Applied Toxicology, 25, 451 58. 

Kubicka-Muranyi M, Goebels R, Goebel C, Uetrecht J, Gleichmann E. T l5nnphocytes ignore procainamide, but respond to its reactive metabolites in peritoneal cells Demonstration by the adoptive transfer popliteal lymph node assay. Toxicol Appl Pharmacol 1993 122 88-94. 

The adverse effects of D-penicillamine in animals are similar to those observed in humans. A study on the effects of D-penicillamine in various strains of mice indicated that D-penicillamine facilitates the induction of autoantibodies in animals with an inherent susceptibility to autoimmunity (Brik et al., 1995). Studies using the popliteal lymph node assay demonstrated that D-penicillamine is capable of inducing an antigen (i.e. compound)-specific T cell response controlled by non-MHC as well as MHC-linked genetic loci (Hurtenbach et al., 1987). 

A number of experiments performed thereafter were supportive for the immune-based etiology of zimeldine-induced adverse effects (Kristofferson Nilsson, 1989). Three individuals occupationally exposed to zimeldine developed allergy to the compound and showed positive patch and skin prick tests and positive response to zimeldine in the lymphocyte transformation test. Patients with a history of zimeldine-induced disease showed marked lymphocyte transformation test responses to zimeldine as well as two metabolites (norzimeldine and CPP200). These findings indicate that zimeldine may be immunogenic indeed, zimeldine has been shown to be positive in the popliteal lymph node assay, based on cell numbers and including germinal centre formation and production of IgM and IgG antibodies (Thomas et al., 1989). 

Primary, secondary, and adoptive popliteal lymph node assays and the lymph node proliferation assay... 

The primary popliteal lymph node assay, in which lymph node weight, cell number, or proliferation of lymph node cells is used as a... 

In the secondary popliteal lymph node assay, pretreated animals are re-exposed to the same chemical or to a metabolite in a dose that itself is incapable of stimulating naive T cells. A measured response to this low dose strongly indicates, but does not formally prove, that memory T cells are present. Proof for the formation of memory T cells can be obtained with the adoptive transfer popliteal lymph node assay in which purified T cells obtained from systemically treated mice are transferred to naive recipients that subsequently receive an injection into the paw of a non-sensitizing dose of the same chemical or a relevant metabolite. 

Reporter antigen popliteal lymph node assay... 

Popliteal lymph node assay as predictive assay... 

In summary, high priority has to be given to the validation of the popliteal lymph node assay (or other local lymph node approaches) and to the further development of predictive animal assays using routes of exposure that are more directly relevant to the human experience. These advancements would significantly enhance the usefulness of animal models and testing strategies for autoimmunity and autoimmune diseases. 

---