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

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.

[1]  R. Hohlfeld,et al.  Autoaggressive myocytotoxic T lymphocytes expressing an unusual gamma/delta T cell receptor , 1992, The Journal of experimental medicine.

[2]  J. Bluestone,et al.  Requirement for positive selection of gamma delta receptor-bearing T cells , 1991, Science.

[3]  A. Hayday,et al.  Regulated expression and structure of T cell receptor gamma/delta transcripts in human thymic ontogeny. , 1991, The EMBO journal.

[4]  S. Tonegawa,et al.  Extrathymic origin of intestinal intraepithelial lymphocytes bearing T-cell antigen receptor gamma delta. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[5]  S. Tonegawa,et al.  Selection of gamma delta T cells with canonical T-cell antigen receptors in fetal thymus. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[6]  M. Krangel,et al.  A distinct wave of human T cell receptor gamma/delta lymphocytes in the early fetal thymus: evidence for controlled gene rearrangement and cytokine production , 1990, The Journal of experimental medicine.

[7]  R. Crystal,et al.  Diversity in junctional sequences associated with the common human V gamma 9 and V delta 2 gene segments in normal blood and lung compared with the limited diversity in a granulomatous disease , 1990, The Journal of experimental medicine.

[8]  S. Carding,et al.  Characterization of γ/δ T cell clones isolated from human fetal liverand thymus , 1990 .

[9]  J. Seidman,et al.  Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein. , 1990, Science.

[10]  J. Strominger,et al.  Evidence for extrathymic changes in the T cell receptor gamma/delta repertoire , 1990, The Journal of experimental medicine.

[11]  J. Bluestone,et al.  Self-reactive γδ T cells are eliminated in the thymus , 1990, Nature.

[12]  M. Krangel,et al.  A Distinct Wave of Human T Cell Receptor Y/b Lymphocytes in the Early Fetal Thymus: Evidence for Controlled Gene Rearrangement and Cytokine Production , 1990 .

[13]  Morita,et al.  Evidence for Extrathymic Changes in the T Cell Receptor Y/b Repertoire , 1990 .

[14]  A. Lanzavecchia,et al.  Molecular analysis of human gamma/delta+ clones from thymus and peripheral blood , 1989, The Journal of experimental medicine.

[15]  S. Tonegawa,et al.  Diversity of γδ T-cell receptors on murine intestinal intraepithelial lymphocytes , 1989, Nature.

[16]  M. Krangel,et al.  Diversity and organization of human T cell receptor delta variable gene segments , 1989, The Journal of experimental medicine.

[17]  J. Strominger,et al.  Novel subsets of human T cells (CD4+ CD8+ TCRγδ and CD4− CD8− TCRαβ) and T‐cell development , 1989 .

[18]  J. Allison,et al.  Limited diversity of γδ antigen receptor genes of thy-1+ dendritic epidermal cells , 1988, Cell.

[19]  L. Lanier,et al.  Human T-cell-receptor delta chain: genomic organization, diversity, and expression in populations of cells. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[20]  L. Hood,et al.  A T cell clone expresses two T cell receptor α genes but uses one αβ heterodimer for allorecognition and self MHC-restricted antigen recognition , 1988, Cell.

[21]  R. Snider,et al.  Signal transduction of gamma/delta T cell antigen receptor with a novel mitogenic anti-delta antibody. , 1988, Journal of immunology.

[22]  G. Pantaleo,et al.  A monoclonal antibody specific for a common determinant of the human T cell receptor gamma/delta directly activates CD3+WT31- lymphocytes to express their functional program(s) , 1988, The Journal of experimental medicine.

[23]  J. Mclean,et al.  Extensive junctional diversity of rearranged human T cell receptor delta genes. , 1988, Science.

[24]  C. Janeway,et al.  Specificity and function of T cells bearing γδ receptors , 1988 .

[25]  Mark M. Davis,et al.  Identification and sequence of a fourth human T cell antigen receptor chain , 1987, Nature.

[26]  J. Seidman,et al.  Identification of a putative second T-cell receptor , 1986, Nature.

[27]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[28]  S. Itohara.  Selection of yS T cells with canonical T-cell antigen receptors in fetal thymus , 2022 .