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Role of coreceptors in positive selection and lineage commitment
S H Chan1, C Waltzinger, A Baron
1Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Faculté de Médecine, Strasbourg.
The EMBO Journal
|October 3, 1994
Summary
Coreceptors are essential for T cell selection, guiding CD4 or CD8 lineage commitment. Manipulating CD8 expression in mice demonstrates coreceptors
Area of Science:
- Immunology
- T cell biology
- Molecular and Cellular Biology
Background:
- The stochastic/selective model explains T lymphocyte positive selection.
- A revised model proposes two MHC engagements for lineage commitment.
Purpose of the Study:
- To investigate the role of coreceptors in T cell positive selection.
- To examine coreceptor function in both stages of thymocyte differentiation.
Main Methods:
- Mice deficient in MHC class II were crossed with CD8-negative or CD8 transgene-carrying mice.
- CD8 expression was manipulated to study its effect on T cell selection.
- Transgenic mice with altered CD8 alpha and beta chains were utilized.
Main Results:
- Coreceptors are required for both stages of positive selection.
- Artificial CD8 expression can rescue T cells that incorrectly chose a lineage.
- Commitment to the CD4 lineage is linked to the helper T cell phenotype.
Conclusions:
- Coreceptors play a critical role throughout T cell positive selection.
- The findings support the revised stochastic/selective model of T cell development.
- This research provides insights into T cell differentiation and lineage commitment.