title: CD4 T cells with effector memory phenotype and function develop in the sterile environment of the fetus.
abstract: 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.
authors.affiliation: Régulation Immunitaire et Vaccinologie, Institut Pasteur, F-75724 Paris, France. INSERM U1041, F-75724 Paris, France. Unit of Innate Defense and Immune Modulation, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Régulation Immunitaire et Vaccinologie, Institut Pasteur, F-75724 Paris, France. INSERM U1041, F-75724 Paris, France.
authors.forename: Brian
authors.initials: B
authors.lastname: Mozeleski
authors.affiliation: Régulation Immunitaire et Vaccinologie, Institut Pasteur, F-75724 Paris, France. INSERM U1041, F-75724 Paris, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Lemoine
authors.affiliation: Régulation Immunitaire et Vaccinologie, Institut Pasteur, F-75724 Paris, France. INSERM U1041, F-75724 Paris, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Dériaud
authors.affiliation: Department Immunology, Institut Pasteur, F-75724 Paris, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Lim
authors.affiliation: Régulation Immunitaire et Vaccinologie, Institut Pasteur, F-75724 Paris, France. INSERM U1041, F-75724 Paris, France.
authors.forename: Dania
authors.initials: D
authors.lastname: Zhivaki
authors.affiliation: Department of Obstetrics and Gynecology, Hospital Bichat Claude Bernard, 75018 Paris, France. Paris 7 Diderot University, F-75013 Paris, France.
authors.forename: Elie
authors.initials: E
authors.lastname: Azria
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Obstetrics and Gynecology, Maternité Port Royal, F-75014 Paris, France. Université Paris Descartes, Sorbonne Paris Cité, F-75005 Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Le Ray
authors.affiliation: INSERM CIC1417, F-75014 Paris, France.
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Roguet
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, F-75005 Paris, France. INSERM CIC1417, F-75014 Paris, France. AP-HP, Hopital Cochin, F-75014 Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Launay
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, F-75013 Paris, France. CNRS, UMR7592, Institut Jacques Monod, F-75013 Paris, France. Atelier de Bio Informatique, F-75005 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vanet
authors.affiliation: Régulation Immunitaire et Vaccinologie, Institut Pasteur, F-75724 Paris, France. INSERM U1041, F-75724 Paris, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Leclerc
authors.affiliation: Régulation Immunitaire et Vaccinologie, Institut Pasteur, F-75724 Paris, France. INSERM U1041, F-75724 Paris, France. richard.lo-man@pasteur.fr.
authors.forename: Richard
authors.initials: R
authors.lastname: Lo-Man
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005333:Fetus / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping