title: Invariant natural killer T cells developing in the human fetus accumulate and mature in the small intestine.
abstract: Invariant natural killer T (iNKT) cells are CD1d-restricted immunoregulatory lymphocytes that share characteristics of both the innate and adaptive immune systems. Although it has been reported that iNKT cells are present in the human fetal thymus, it is currently unknown how they distribute, differentiate, and function in fetal peripheral lymphoid and non-lymphoid organs. Here, we show that functional human fetal iNKT cells develop and differentiate in a tissue-specific manner during the second trimester. Fetal iNKT cells accumulated in the small intestine, where they gained a mature phenotype and mounted robust interferon (IFN)-γ responses. In contrast, iNKT cells in the spleen and mesenteric lymph nodes were less frequently detected, less differentiated, mounted poor IFN-γ responses, but proliferated vigorously upon stimulation with α-galactosylceramide. These data demonstrate that fetal iNKT cells can differentiate and acquire potent effector functions in utero before the establishment of the commensal microflora.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: L
authors.initials: L
authors.lastname: Loh
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: M A
authors.initials: MA
authors.lastname: Ivarsson
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Michaëlsson
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: J K
authors.initials: JK
authors.lastname: Sandberg
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Nixon
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D005333:Fetus / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D008214:Lymphocytes / Q000276:immunology; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000276:immunology
chemical_list: D007371:Interferon-gamma