CD4 T cells with effector memory phenotype and function develop in the sterile environment of the fetus. - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Science Translational Medicine Année : 2014

CD4 T cells with effector memory phenotype and function develop in the sterile environment of the fetus.

Résumé

The T cell compartment is considered to be naïve and dedicated to the development of tolerance during fetal development. We have identified and characterized a population of fetally developed CD4 T cells with an effector memory phenotype (TEM), which are present in cord blood. This population is polyclonal and has phenotypic features similar to those of conventional adult memory T cells, such as CD45RO expression. These cells express low levels of CD25 but are distinct from regulatory T cells because they lack Foxp3 expression. After T cell receptor activation, neonatal TEM cells readily produced tumor necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF). We also detected interferon-γ (IFN-γ)-producing T helper 1 (TH1) cells and interleukin-4 (IL-4)/IL-13-producing TH2-like cells, but not IL-17-producing cells. We used chemokine receptor expression patterns to divide this TEM population into different subsets and identified distinct transcriptional programs using whole-genome microarray analysis. IFN-γ was found in CXCR3(+) TEM cells, whereas IL-4 was found in both CXCR3(+) TEM cells and CCR4(+) TEM cells. CCR6(+) TEM cells displayed a genetic signature that corresponded to TH17 cells but failed to produce IL-17A. However, the TH17 function of TEM cells was observed in the presence of IL-1β and IL-23. In summary, in the absence of reported pathology or any major infectious history, T cells with a memory-like phenotype develop in an environment thought to be sterile during fetal development and display a large variety of inflammatory effector functions associated with CD4 TH cells at birth.
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Dates et versions

hal-01060153 , version 1 (03-09-2014)

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Xiaoming Zhang, Brian Mozeleski, Sebastien Lemoine, Edith Dériaud, Annick Lim, et al.. CD4 T cells with effector memory phenotype and function develop in the sterile environment of the fetus.. Science Translational Medicine, 2014, 6 (238), pp.238ra72. ⟨10.1126/scitranslmed.3008748⟩. ⟨hal-01060153⟩
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