PT - JOURNAL ARTICLE AU - Zhang, Xiaoming AU - Mozeleski, Brian AU - Lemoine, Sebastien AU - Dériaud, Edith AU - Lim, Annick AU - Zhivaki, Dania AU - Azria, Elie AU - Le Ray, Camille AU - Roguet, Gwenaelle AU - Launay, Odile AU - Vanet, Anne AU - Leclerc, Claude AU - Lo-Man, Richard TI - CD4 T Cells with Effector Memory Phenotype and Function Develop in the Sterile Environment of the Fetus AID - 10.1126/scitranslmed.3008748 DP - 2014 May 28 TA - Science Translational Medicine PG - 238ra72--238ra72 VI - 6 IP - 238 4099 - http://stm.sciencemag.org/content/6/238/238ra72.short 4100 - http://stm.sciencemag.org/content/6/238/238ra72.full AB - 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.