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.
Stolzer
Amy L
AL
The Laboratory of T cell Immunobiology, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Sadelain
Michel
M
Sant'Angelo
Derek B
DB
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000473:pathology; D022761:Gene Transfer, Horizontal; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000502:physiology; D012190:Retroviridae / Q000235:genetics; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology; D014161:Transduction, Genetic
D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007371:Interferon-gamma