Local lymph node assays development

Kimber, I. et al, The local lymph node assay Developments and applications. Toxicology, 93, 13, 1994. 

Kimber I, Dearman RJ, Scholes EW, Basketter DA (1994) The local lymph node assay developments and applications. Toxicology 93 13-31... 

Kimber, I. and Weisenberger, C., A murine local lymph node assay for the identification of contact allergens. Assay development and results of an initial validation study, Arch. Toxicol., 63, 274, 1989. 

The most important advance in ACD testing has been the development of the murine local lymph node assay (LLNA). Although the general concept originated in the 1960s,... 

Organisation of Economic Cooperation and Development, OECD Guideline for the Testing of Chemicals. Skin Sensitisation Local Lymph Node Assay, No. 429, Paris, 2002. 

Kimber, I., Mitchell, J.A. and Griffin, A.C. (1986). Development of murine local lymph node assay for the determination of sensitising potential. Fd. Chem. Toxicol. 24 585-586. 

This test uses an in vitro human dendritic cell culture to obtain information of the potential for various chemicals to induce allergic contact dermatitis. This test is used as an alternative to the Local Lymph node assay (LLNA) to minimize or replace the use of live animal testing for predicting skin sensitization (Kimber et al. 2002, see below). The test allows for evaluation of skin sensitization by examining the presence of cell surface markers on Periperal Blood Mononuclear Cell (PBMC)-derived dendritic cells (DC) that are known to be involved in the development of allergic contact dermatitis. 

Kimber I, Basketter DA (1992) The murine local lymph node assay acommentary on collaborative studies and new directions. Fd Chem Toxicol 30 165-169 Kimber I, Dearman RJ, Scholes EW, Basketter DA (1994) The local nymph node assay developments and applications. Toxicology 93 13-31... 

Recently, a more economical, less subjective test for contact hypersensitivity has been developed using mice. This test, the local lymph node assay (LLNA), assesses the proliferative response of lymphocytes in the draining lymph node following appli-... 

OECD (2002) Local lymph node assay. Test Guideline no 429. Organisation for Economic Cooperation and Development, Paris... 

Up to now, pulmonary sensitization cannot be examined in animal tests. For the examination of dermal sensitization, different test methods with different sensitiveness are available. For the examination of industrial chemicals, the so-caUed patch test applied to guinea pigs is usually sufficiently sensitive. In this, the test substance is administered directly to the skin, as in the human exposure situation. The maximization test, also called the Magnusson-Kligmann test (see Fig. 2.7) and developed originally for cosmetics and pharmaceuticals, is nowadays more and more used for chemicals also. A recently developed test method is the local lymph node assay (LLNA), which can be used to examine the potency of an allergen. 

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. 

Several immune function assays measuring lymphocyte proliferation and antibody production to experimental antigens have been developed as surrogates for measuring protective immune responses. Mice exposed to carbon dust inhalation (2-4 mg/m ) had a decreased number of antibody-forming cells in the spleen that was proportional to exposure time (64). In local mediastinal lymph nodes... 

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