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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
CCR7 expression in developing thymocytes is linked to the CD4 versus CD8 lineage decision
Xinye Yin1, Ena Ladi, Shiao Wei Chan
1Department of Molecular and Cell Biology, Division of Immunology, University of California, Berkeley, CA 94720, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|November 21, 2007
Summary
T cell development involves positive selection, guiding T cell fate. This study reveals chemokine receptor CCR7 timing during selection influences T cell lineage commitment and CD8 T cell development.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- T cell progenitors mature in the thymus through positive selection.
- T cell receptor (TCR) binding to MHC ligands dictates T cell lineage (CD4 or CD8).
- Chemokine receptor CCR7 mediates thymocyte migration during positive selection.
Purpose of the Study:
- To investigate the role of CCR7 expression timing in T cell lineage commitment.
- To understand how CCR7 up-regulation relates to MHC class I (MHC-I) and MHC class II (MHC-II) selection.
- To explore the impact of Th-POK mutations on CCR7 expression and T cell development.
Main Methods:
- Analysis of CCR7 expression in CD4(+)CD8(+) thymocytes during positive selection.
- Examination of CCR7 levels in mice with Th-POK mutations.
- Assessment of T cell development upon CCR7 overexpression.
Main Results:
- CCR7 up-regulation is higher in thymocytes selected by MHC-I compared to MHC-II.
- Th-POK mutations lead to increased CCR7 expression in MHC-II-selected thymocytes.
- CCR7 overexpression promotes CD8 T cell development even with MHC-II-specific TCRs.
Conclusions:
- The timing of CCR7 expression, relative to coreceptor down-regulation, is controlled by lineage commitment signals.
- CCR7 plays a critical role in regulating T cell lineage decisions during thymic development.
- These findings offer insights into the molecular mechanisms governing T cell fate determination.
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