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Regulación mediada por linfotoxinas de la diferenciación de las células gamma delta por los progenitores de las
Bruno Silva-Santos1, Daniel J Pennington, Adrian C Hayday
1Peter Gorer Department of Immunobiology, Guy's King's St. Thomas' Medical School, King's College, Guy's Hospital, London SE1 9RT, UK.
Science (New York, N.Y.)
|December 14, 2004
Resumen
Los timocitos dobles positivos (DP) regulan el desarrollo temprano de las células T, incluidas las células T gammadelta, a través de la señalización de los receptores RORgt y beta de linfotoxina. Esto sugiere una integración coordinada de los linajes de células T alfabeta y gammadelta dentro del timo.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología del desarrollo Biología del desarrollo.
- Biología celular Biología celular.
Sus antecedentes:
- El timo genera linajes de células T alfabeta y gammadelta, que tradicionalmente se considera que se desarrollan de forma independiente.
- Los timocitos doblemente positivos (DP) (que expresan CD4 y CD8) son vistos principalmente como precursores de las células T alphabeta.
Objetivo del estudio:
- Investigar el papel de los timocitos DP en la regulación de la diferenciación temprana de las células T progenitoras y el desarrollo de las células T gammadelta.
- Aclarar los mecanismos moleculares subyacentes a la regulación mediada por células DP de la integración del linaje de células T.
Principales métodos:
- Análisis de las vías de diferenciación de timocitos.
- Investigando la participación del factor de transcripción RORgt.
- Estudiando el papel de la vía de señalización del receptor beta de linfotoxina (LTbetaR).
Principales resultados:
- Los timocitos DP regulan activamente la diferenciación de los primeros progenitores de los timocitos.
- Las células DP influyen en el desarrollo de las células T gammadelta.
- Esta regulación depende de la señalización del factor de transcripción RORgt y LTbetaR.
Conclusiones:
- Los timocitos DP no son simplemente progenitores, sino que regulan activamente el desarrollo del linaje de células T.
- Un modelo revisado de la función del timo involucra procesos de tipo inducción del tejido linfoide que coordinan la integración de las células T alfabeta y gammadelta.
- Esto pone de relieve un nuevo mecanismo para el desarrollo y la integración funcional de distintos linajes de células T.
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