A distinct wave of human T cell receptor gamma/delta lymphocytes in the early fetal thymus: evidence for controlled gene rearrangement and cytokine production.
The rearrangement and expression of human T cell receptor (TCR)-gamma and -delta gene segments in clonal and polyclonal populations of early fetal and postnatal human TCR-gamma/delta thymocytes were examined. The data suggest that the TCR-gamma and -delta loci rearrange in an ordered and coordinated fashion. Initial rearrangements at the TCR-delta locus join V delta 2 to D delta 3, and initial rearrangements at the TCR-gamma locus join downstream V gamma gene segments (V gamma 1.8 and V gamma 2) to upstream J gamma gene segments associated with C gamma 1. These rearrangements are characterized by minimal junctional diversity. At later times there is a switch at the TCR-delta locus such that V delta 1 is joined to upstream D delta gene segments, and a switch at the TCR-gamma locus such that upstream V gamma gene segments are joined to downstream J gamma gene segments associated with C gamma 2. These rearrangements are characterized by extensive junctional diversity. Programmed rearrangement explains in part the origin of discrete subpopulations of peripheral blood TCR-gamma/delta lymphocytes that have been defined in previous studies. In addition, cytokine production by early fetal and postnatal TCR-gamma/delta thymocyte clones was examined. Fetal thymocyte clones produced significant levels of IL-4 and IL-5 following stimulation, whereas postnatal thymocyte clones did not produce these cytokines. Thus, these cell populations may represent functionally distinct subsets as well.
Krangel
M S
MS
Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Yssel
H
H
Brocklehurst
C
C
Spits
H
H
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D001685:Biological Factors / Q000096:biosynthesis*; D002648:Child; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D016207:Cytokines; D005333:Fetus; D005455:Fluorescent Antibody Technique; D015329:Gene Rearrangement, T-Lymphocyte; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001685:Biological Factors; D003115:Colony-Stimulating Factors; D016207:Cytokines; D006133:Growth Substances; D007127:Immunoglobulin Constant Regions; D007135:Immunoglobulin Variable Region; D007378:Interleukins; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor