title: Human fetal liver gamma/delta T cells predominantly use unusual rearrangements of the T cell receptor delta and gamma loci expressed on both CD4+CD8- and CD4-CD8- gamma/delta T cells.
abstract: Substantial numbers of both alpha/beta and gamma/delta T cells are present in human fetal liver, which suggests a role of the fetal liver in T cell development. The diversity of fetal liver T cell receptor (TCR) gamma and delta chain rearrangements was examined among both CD4+CD8- and CD4-CD8- gamma/delta T cell clones. In addition, TCR delta chain transcripts from three fetal livers were sequenced after polymerase chain reaction amplification of TCR delta chains with V delta 1 or V delta 2 rearrangements. Five of six fetal liver gamma/delta T cell clones had a V delta 2-D delta 3-J delta 3 gene rearrangement with limited junctional diversity; three of these clones had an unusual CD4+CD8- phenotype. V delta 2-D delta 3-J delta 3 gene rearrangements were also common among both in-frame and out-of-frame transcripts from three fetal livers, indicating that they are the result of an ordered rearrangement process. TCR gamma chain sequences of the fetal liver gamma/delta T cell clones revealed V gamma 1-J gamma 2.3, V gamma 2-J gamma 1.2, and V gamma 3-J gamma 1.1 rearrangements with minimal incorporation of template-independent N region nucleotides. TCR gamma chain rearrangements found in these fetal liver T cell clones were different from those that have been observed among early thymic gamma/delta T cell populations, while similar TCR delta chain rearrangements are found among gamma/delta T cells from both sites. These data demonstrate that the fetal liver harbors gamma/delta T cell populations distinct from those found in the fetal thymus, suggesting that the fetal liver is a site of gamma/delta T cell development in humans. These unusual T cell populations may serve a specific function in the fetal immune system.
authors.affiliation: Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: K W
authors.initials: KW
authors.lastname: Wucherpfennig
authors.forename: Y J
authors.initials: YJ
authors.lastname: Liao
authors.forename: M
authors.initials: M
authors.lastname: Prendergast
authors.forename: J
authors.initials: J
authors.lastname: Prendergast
authors.forename: D A
authors.initials: DA
authors.lastname: Hafler
authors.forename: J L
authors.initials: JL
authors.lastname: Strominger
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D008099:Liver / Q000196:embryology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D009838:Oligodeoxyribonucleotides; D016692:Receptors, Antigen, T-Cell, gamma-delta