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

AL Stolzer, M Sadelain… - European journal of …, 2005 - Wiley Online Library
AL Stolzer, M Sadelain, DB Sant'Angelo
European journal of immunology, 2005Wiley Online Library
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‐Au, cause rapid onset of experimental autoimmune …
Abstract
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‐Au, 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.
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