Human CD4(+)CD25(+) cells: a naturally occurring population of regulatory T cells.
Blood
; 98(9): 2736-44, 2001 Nov 01.
Article
en En
| MEDLINE
| ID: mdl-11675346
ABSTRACT
Despite thymic deletion of cells with specificity for self-antigens, autoreactive T cells are readily detectable in the normal T-cell repertoire. In recent years, a population of CD4(+) T cells that constitutively express the interleukin-2 receptor-alpha chain, CD25, has been shown to play a pivotal role in the maintenance of self-tolerance in rodent models. This study investigated whether such a regulatory population exists in humans. A population of CD4(+)CD25(+) T cells, taken from the peripheral blood of healthy individuals and phenotypically distinct from recently activated CD4(+) T cells, was characterized. These cells were hyporesponsive to conventional T-cell stimuli and capable of suppressing the responses of CD4(+)CD25(-) T cells in vitro. Addition of exogenous interleukin-2 abrogated the hyporesponsiveness and suppressive effects of CD4(+)CD25(+) cells. Suppression required cell-to-cell contact but did not appear to be via the inhibition of antigen-presenting cells. In addition, there were marked changes in the expression of Notch pathway molecules and their downstream signaling products at the transcriptional level, specifically in CD4(+)CD25(+) cells, suggesting that this family of molecules plays a role in the regulatory function of CD4(+)CD25(+) cells. Cells with similar phenotype and function were detected in umbilical venous blood from healthy newborn infants. These results suggest that CD4(+)CD25(+) cells represent a population of regulatory T cells that arise during fetal life. Comparison with rodent CD4(+)CD25(+) cells suggests that this population may play a key role in the prevention of autoimmune diseases in humans.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Linfocitos T CD4-Positivos
/
Receptores de Interleucina-2
/
Subgrupos de Linfocitos T
/
Autotolerancia
/
Receptores de Superficie Celular
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Humans
/
Newborn
Idioma:
En
Revista:
Blood
Año:
2001
Tipo del documento:
Article
País de afiliación:
Reino Unido