Molecular signals involved in CD4 versus CD8 T cell commitment
Por:
Nava K., Soldevila G.
Publicada:
1 ene 2004
Resumen:
During T cell development in the thymus, differentiation and selection processes take place to ensure the generation of a restricted self-tolerant T cell repertoire with the ability to recognize and eliminate foreign pathogens. Thymocytes that recognise self peptides on self MHC molecules with low avidity are rescued from programmed cell death and are positively selected, while those thymocytes recognising self peptide-MHC complexes with high avidity are deleted by negative selection. It is known that signals transduced through the T Cell Receptor are crucial for the survival and differentiation of immature thymocytes, during positive selection. One of the most important events during this selection process is the choice of a specific T cell lineage, to become a helper CD4 T cell or a cytotoxic CD8 T cell. The molecular events involved in this choice are still on debate. The initial models described to explain this selection process were known as the «instructive » and the «stochastic» models, both of which have found experimental evidence in favour and against. However, a «strength of signal» model, based on the intensity and/or duration of the TCR-MHC/peptide interaction has recently acquired more support. Finally we also describe a new model called "kinetic signalling" model which offers a new perspective of the mechanisms by which T cell commitment takes place in the thymus. In this review, we will also discuss the current knowledge about the molecular mechanisms involved in CD4 versus CD8 lineage commitment, including signalling and transcriptional pathways, which have been postulated to participate in this differentiation process.
Filiaciones:
Nava K.:
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, UNAM, Circuito Escolar s/n, Apartado Postal 70228, México DF-04510, Mexico
Soldevila G.:
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, UNAM, Circuito Escolar s/n, Apartado Postal 70228, México DF-04510, Mexico
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