A novel subset of adult gamma delta thymocytes that secretes a distinct pattern of cytokines and expresses a very restricted T cell receptor repertoire.
We have characterized the function, phenotype, ontogenic development, and T cell receptor (TCR) repertoire of a subpopulation of gamma delta thymocytes, initially defined by expressing low levels of Thy-1, that represents around 5% and 30% of total gamma delta thymocytes in adult C57BL/6 and DBA/2 mice, respectively. Activation of FACS-sorted Thy-1dull gamma delta thymocytes from DBA/2 mice with anti-gamma delta monoclonal antibodies in the presence of interleukin-2 (IL-2) results in the secretion of high levels of several cytokines, including interferon-gamma (IFN-gamma), IL-4, IL-10, and IL-3. In contrast, only IFN-gamma was detected in parallel cultures of Thy-1bright gamma delta thymocytes. Virtually all Thy-1dull gamma delta thymocytes express high levels of CD44 and low levels of the heat-stable antigen and CD62 ligand, while around half of them express the NK1.1 marker. Thy-1dull gamma delta thymocytes are barely detectable in newborn animals, and their representation increases considerably during the first 2 weeks of postnatal life. The majority of Thy-1dull gamma delta thymocytes from DBA/2 mice express TCR encoded by the V gamma 1 gene and a novel V delta 6 gene named V delta 6.4. Sequence analysis of these functionally rearranged gamma and delta genes revealed highly restricted V delta-D delta-J delta junctions, and somewhat more diverse V gamma-J gamma junctions. We conclude that Thy-1dull gamma delta thymocytes exhibit properties that are equivalent to those of natural killer TCR alpha beta T cells. Both cell populations produce the same distinct pattern of cytokines upon activation, share a number of phenotypic markers originally defined for activated or memory T cells, display similar postnatal kinetics of appearance in the thymus and express a very restricted TCR repertoire.
Azuara
V
V
Unité d'Immunobiologie, Centre National de la Recherche Scientifique URA 1961, Institut Pasteur, Paris, France.
Levraud
J P
JP
Lembezat
M P
MP
Pereira
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D006825:Hybridomas; D016753:Interleukin-10 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D018800:Thy-1 Antigens / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*
D016207:Cytokines; D007377:Interleukin-3; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018800:Thy-1 Antigens; D016753:Interleukin-10; D015847:Interleukin-4