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 child's play a pivotal office inward 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. Due to the lack of a specific marker for Treg cells, a combination of CD4, CD25, and FoxP3 is commonly used for their identification.
Addition of exogenous interleukin-2 abrogated the hyporesponsiveness and suppressive consequences 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 nerve pathway corpuscles and their downstream signaling products at the transcriptional level, specifically in CD4(+)CD25(+) cells, indicating that this crime syndicate of molecules bets a office 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 child's play a Francis Scott Key theatrical role in the prevention of autoimmune diseases in humans.
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