RESUMO
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.
Assuntos
Encefalomielite Autoimune Experimental/etiologia , Transferência Genética Horizontal , Receptores de Antígenos de Linfócitos T/genética , Animais , Encefalomielite Autoimune Experimental/patologia , Interferon gama/biossíntese , Interleucina-4/biossíntese , Camundongos , Proteína Básica da Mielina/imunologia , Receptores de Antígenos de Linfócitos T/fisiologia , Retroviridae/genética , Baço/imunologia , Linfócitos T/fisiologia , Transdução GenéticaRESUMO
Using genetic and phenotypic analyses, we have analyzed the developmental pathway of mouse CD1d-restricted invariant NKT cells. We provide strong evidence that similar to conventional T cells, positive selection of NKT cells occurs during a CD4(+)CD8(+) stage. Later stages of NKT cell development involved the down-regulation of both TCR and CD4 levels and therefore diverge from conventional T cell development pathways. A unique and complete dependency for development on Fyn, a Src family kinase member, also distinguishes the NKT cell and conventional T cell populations.