Human fetal liver γ/δ T cells predominantly use unusual rearrangements of the T cell receptor δ and γ loci expressed on both CD4+CD8- and CD4-CD8- γ/δ T cells

Abstract

Substantial numbers of both α/β and γ/δ 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) γ and δ chain rearrangements was examined among both CD4+CD8- and CD4-CD8- γ/δ T cell clones. In addition, TCR δ chain transcripts from three fetal livers were sequenced after polymerase chain reaction amplification of TCR δ chains with Vδ1 or Vδ2 rearrangements. Five of six fetal liver γ/δ T cell clones had a Vδ2-Dδ3-Jδ3 gene rearrangement with limited junctional diversity; three of these clones had an unusual CD4+CD8- phenotype. Vδ2-Dδ3-Jδ3 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 γ chain sequences of the fetal liver γ/δ T cell clones revealed Vγ1-Jγ2.3, Vγ2-Jγ1.2, and Vγ3-Jγ1.1 rearrangements with minimal incorporation of template-independent N region nucleotides. TCR γ chain rearrangements found in these fetal liver T cell clones were different from those that have been observed among early thymic γ/δ T cell populations, while similar TCR δ chain rearrangements are found among γ/δ T cells from both sites. These data demonstrate that the fetal liver harbors γ/δ T cell populations distinct from those found in the fetal thymus, suggesting that the fetal liver is a site of γ/δ T cell development in humans. These unusual T cell populations may serve a specific function in the fetal immune system.