Extrathymic origin of human gamma delta T cells during fetal development.
We have identified the first TCRs to be generated in vivo during normal human fetal development. Before thymic formation, the liver is a site of generation for a subset of V gamma 9/V delta 2+ gamma delta T cells. Analysis of the expression of the male-specific gene, SRY, by V gamma 9/V delta 2+ gamma delta T cells isolated from the fetal liver of male donors has shown that these cells are generated de novo in the liver. Examination of TCR-V gamma and -V delta gene expression demonstrated that although multiple receptor rearrangements could be detected, V gamma 9-JP- and V delta 2-D delta 3-J delta 1/3-encoded receptors were preferentially expressed in each of five individual liver samples. Structural analysis of these receptor chains and those expressed by a panel of V gamma 9/V delta 2+ fetal T cell clones showed that the V gamma 9-JP receptors were invariant or canonical and that the delta-chains contained non-germ line-encoded structural motifs. gamma delta T cells expressing these structurally limited receptor chains were shown to be functional and capable of responding to mycobacterial Ags. Together with the observation that V gamma 9/V delta 2+ cells represented the majority of T cells present in the fetal liver between 7 and 11 wk of development, our findings demonstrate that this subset of gamma delta T cells is a major, and presumably important, component of the human fetal immune system.
McVay
L D
LD
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Carding
S R
SR
D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000276:immunology; D005333:Fetus / Q000276:immunology*; D018507:Gene Expression Regulation, Developmental; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006411:Hematopoiesis, Extramedullary; D006801:Humans; D008099:Liver / Q000166:cytology / Q000196:embryology; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D051876:Sex-Determining Region Y Protein; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors