title: Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero.
abstract: As the immune system develops, T cells are selected or regulated to become tolerant of self antigens and reactive against foreign antigens. In mice, the induction of such tolerance is thought to be attributable to the deletion of self-reactive cells. Here, we show that the human fetal immune system takes advantage of an additional mechanism: the generation of regulatory T cells (Tregs) that suppress fetal immune responses. We find that substantial numbers of maternal cells cross the placenta to reside in fetal lymph nodes, inducing the development of CD4+CD25highFoxP3+ Tregs that suppress fetal antimaternal immunity and persist at least until early adulthood. These findings reveal a form of antigen-specific tolerance in humans, induced in utero and probably active in regulating immune responses after birth.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California at San Francisco (UCSF), San Francisco, CA 94110, USA.
authors.forename: Jeff E
authors.initials: JE
authors.lastname: Mold
authors.forename: Jakob
authors.initials: J
authors.lastname: Michaëlsson
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Burt
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Muench
authors.forename: Karen P
authors.initials: KP
authors.lastname: Beckerman
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Tzong-Hae
authors.initials: TH
authors.lastname: Lee
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
mesh_terms: D000293:Adolescent; D000938:Antigen-Presenting Cells / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D046528:Chimerism; D005260:Female; D005333:Fetus / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007108:Immune Tolerance; D007519:Isoantigens / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D015291:Transforming Growth Factors / Q000235:genetics / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007519:Isoantigens; D048069:Tumor Necrosis Factors; D015291:Transforming Growth Factors