The purpose of this proposal is to test the hypothesis that mouse strains that are genetically susceptible to the induction of experimental allergic encephalomyelitis (EAE) i.e. SJL/J) have cellular and/or environmental defects that allow for the generation of abnormal T cells which are not present in strains that are genetically EAE- resistant (i.e. B10.S). In order to do, the following questions will be addressed: 1) Is the susceptibility of SJL/J mice to EAE induction due to an intrinsic defect at the prothymocyte level and/or the microenvironment in which these cells mature? 2) What is the basis of the resistance of B10.S mice to EAE induction? We will use a quantitative radiation bone marrow chimera system between EAE-susceptible SJL/J (H-2s; thy 1.2) and EAE-resistant B10.S Thy 1.1 (H-2s; Thy 1.1) mice to determine whether SJL/J prothymocytes can transfer the predisposition for the development of EAE to naive B10.S Thy 1.1 recipients and/or whether the SJL/J environment can confer such a predisposition upon B10.S Thy 1.1 prothymocytes maturing under its influence. In addition, we will use in vitro culture, cloning, in situ immunohistochemistry, in vitro priming and adoptive transfer of cultured T cells to naive unirradiated recipients to investigate the basis for the apparent cellular resistance of B10.S/B10.S Thy 1.1 mice to the development of EAE. These strategies should be useful in further elucidating the mechanisms involved in the pathogenesis of EAE, and possibly by extension, multiple sclerosis.
| Burleson, J A; Binder, T A; Goldschneider, I (1993) Use of logistic regression in comparing multiple limiting dilution analyses of antigen-reactive T cells. J Immunol Methods 159:47-52 |
