Coreceptor gene imprinting governs thymocyte lineage fate.
EMBO J
; 31(2): 366-77, 2012 Jan 18.
Article
em En
| MEDLINE
| ID: mdl-22036949
ABSTRACT
Immature thymocytes are bipotential cells that are signalled during positive selection to become either helper- or cytotoxic-lineage T cells. By tracking expression of lineage determining transcription factors during positive selection, we now report that the Cd8 coreceptor gene locus co-opts any coreceptor protein encoded within it to induce thymocytes to express the cytotoxic-lineage factor Runx3 and to adopt the cytotoxic-lineage fate, findings we refer to as 'coreceptor gene imprinting'. Specifically, encoding CD4 proteins in the endogenous Cd8 gene locus caused major histocompatibility complex class II-specific thymocytes to express Runx3 during positive selection and to differentiate into CD4(+) cytotoxic-lineage T cells. Our findings further indicate that coreceptor gene imprinting derives from the dynamic regulation of specific cis Cd8 gene enhancer elements by positive selection signals in the thymus. Thus, for coreceptor-dependent thymocytes, lineage fate is determined by Cd4 and Cd8 coreceptor gene loci and not by the specificity of T-cell antigen receptor/coreceptor signalling. This study identifies coreceptor gene imprinting as a critical determinant of lineage fate determination in the thymus.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Subpopulações de Linfócitos T
/
Antígenos CD8
/
Linfócitos T CD8-Positivos
/
Linfopoese
/
Timócitos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos