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Long-term in vivo provision of antigen-specific T cell immunity by programming hematopoietic stem cells

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Long-term in vivo provision of antigen-specific T cell immunity by programming hematopoietic stem cells
Id. 5040087
Idioma inglés
Titulo Long-term in vivo provision of antigen-specific T cell immunity by programming hematopoietic stem cells
Autor(es) Yang, Lili
Baltimore, David
Localización http://www.pubmedcentral.gov/articlerender.fcgi?artid=553287
Versión 1.0
Estado Final
Descripción A method to genetically program mouse hematopoietic stem cells to develop into functional CD8 or CD4 T cells of defined specificity in vivo is described. For this purpose, a bicistronic retroviral vector was engineered that efficiently delivers genes for both ? and ? chains of T cell receptor (TCR) to hematopoietic stem cells. When modified cell populations were used to reconstruct the hematopoietic lineages of recipient mice, significant percentages of antigen-specific CD8 or CD4 T cells were observed. These cells expressed normal surface markers and responded to peptide antigen stimulation by proliferation and cytokine production. Moreover, they could mature into memory cells after peptide stimulation. Using TCRs specific for a model tumor antigen, we found that the recipient mice were able to partially resist a challenge with tumor cells carrying the antigen. By combining cells modified with CD8- and CD4-specific TCRs, and boosting with dendritic cells pulsed with cognate peptides, complete suppression of tumor could be achieved and even tumors that had become established would regress and be eliminated after dendritic cell/peptide immunization. This methodology of “instructive immunotherapy” could be developed for controlling the growth of human tumors and attacking established pathogens.
Palabras clave Biological Sciences
Tipo de recurso Text
Tipo de Interactividad Expositivo
Nivel de Interactividad muy bajo
Audiencia Estudiante
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Estructura Atomic
Coste no
Copyright
Copyright © 2005, The National Academy of Sciences
Requerimientos técnicos Browser: Any
Fecha de contribución 24-nov-2006
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