Animal Research and T Cell Tolerance
The concept on the humane use of laboratory animals has been developed by the british William Russell and Rex Burch in 1959. "Humane science is good science, and the best way to achieve that is the rigorous application of the 3R´s". The implementation of the 3R´s is very important, but it will not become unnecessary, since non-animal test methods have at the moment their limitations in identifying complex interactions between different cells in a structured organ. Vice versa, in humans samples in autoimmune diseases are often inaccessible and researchers are dependent on the study of peripheral blood lymphocytes, a cell population distant from disease foci and being only partially representative of the pathogenic process.
Studies of animal models have been essential for elucidating the immune reaction in health and disease. They have revealed the principals of immunological self-tolerance and autoimmunity and have led to the development of a large number of clinically applicable immunotherapies, like copaxone, natalizumab, fingolimod.
All animal models however represent only particular aspects of a complex human tolerance induction, and not all animal response patterns are replicated in the human immune system. Models to study the induction of tolerance are needed in areas that exclude purely human studies for ethical or practical reasons. Induction of immunologic tolerance, i.e. the unresponsiveness specific to self- or foreign antigen, is an important feature of the mammal immune system. T cell differentiation in the thymus generates a peripheral repertoire of mature T cells that mounts strong responses to foreign antigens but is largely unresponsive to self-antigens. This state of specific immunological tolerance to self-components involves both central and peripheral mechanisms. If not properly induced and trained, this can result in allergy or autoimmune diseases, such as juvenile onset diabetes mellitus, rheumatoid arthritis and multiple sclerosis. Basic understandings of the molecular mechanisms on tolerance induction have been gained from animal models. Genetic homogeneity and the advantage that mice are protected from any other disease or influence, which are hard-to-control variables in humans, have shed light on some of the most complex issues. An often-mentioned indicator for translational research success has been that most of the projects winning a Nobel prize in medicine and physiology from the field of immunology for the past 30 years have started with research performed with mouse models. It has become clear that rodent share with humans many essential principles, like the process of generating the receptors of T cells and the antibodies of B cells, their antigen recognition system but also the messenger molecules in coordinating immune responses that translation is frequently feasible and productive.