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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Csk controla el desarrollo mediado por el receptor de antígenos y la selección de células del linaje T
C Schmedt1, K Saijo, T Niidome
1Laboratory for Lymphocyte Signalling, University of Cologne, Germany. c.schmedt@uni-koeln.de
Nature
|September 11, 1998
Resumen
La inactivación de la carboxiterminal Src quinasa (Csk) en los timocitos elimina la necesidad de receptores de células T pre-T y alfabetaT (TCR) para el desarrollo de células T. Esto revela el Csksk.
Área de la Ciencia:
- Inmunología Inmunología.
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
Sus antecedentes:
- El desarrollo de las células T se basa en las señales de los receptores de células pre-T (preTCR) y los receptores de células T alfabetizadas (alphabetetaTCR).
- La activación de las proteínas tirosinacinasas (PTK) de la familia Src es crucial después de la participación del receptor, pero su papel preciso en la diferenciación sigue sin estar claro.
- La Src quinasa carboxiterminal (Csk) actúa como un regulador negativo de las PTK de la familia Src.
Objetivo del estudio:
- Investigar el papel de Csk en la regulación de la actividad PTK de la familia Src durante el desarrollo de las células T.
- Determinar si la inactivación de Csk afecta a la dependencia de la diferenciación de las células T en la señalización preTCR y alphabetaTCR.
Principales métodos:
- La inactivación genética de Csk en timocitos inmaduros.
- Análisis del desarrollo de timocitos y poblaciones de células T periféricas utilizando citometría de flujo y análisis de marcadores de superficie celular.
Principales resultados:
- La inactivación de Csk en timocitos inmaduros abrogó el requisito de preTCR, alphabetaTCR y MHC clase II.
- El desarrollo de los timocitos CD4+ 8+ doblemente positivos y CD4+ mono positivos procedió independientemente de la señalización preTCR/alfabetaTCR tras la pérdida de Csk.
- Las células periféricas del linaje CD4 alfa-beta-T se desarrollaron sin depender de estas señales de receptores.
Conclusiones:
- Csk y sus sustratos son esenciales para establecer un control mediado por preTCR/alfabetaTCR sobre el desarrollo de las células T de la familia alfa.
- Csk actúa como un punto de control crítico, asegurando que el desarrollo de las células T depende de la señalización adecuada de los receptores.
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