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.