Fulminant experimental autoimmune encephalo-myelitis induced by retrovirally mediated TCR gene transfer

Although some efforts have been made to direct the antigen specificity of developing T cells by retroviral mediated expression of known TCR, it is not clear if the resultant T cells are fully functional. In this study retroviral gene transfer technology was used to introduce a cDNA encoding the TCR from a known encephalitogenic T cell into the bone marrow of mice. Activated T cells expressing this TCR, which is specific for the Ac1-11 peptide from myelin basic protein presented by I-A(u), cause rapid onset of experimental autoimmune encephalomyelitis (EAE). This enabled us to use the onset and progression of the disease as a direct measure of effector functions of T cells generated by this method. The data presented here show that recipients of bone marrow retrovirally transduced with this TCR rapidly develop full-blown EAE that results in paralysis. Therefore, retroviral TCR delivery into the bone marrow supports the development of T cells into fully functional effector cells.