Human CD4-8- -derived clones. Phenotypic and functional characteristics and variation between donors in patterns of T-cell receptor gamma gene rearrangements.
Clones were derived from highly purified human CD4-8- lymphocytes from three different donors and maintained in the presence of interleukin 2 and phytohaemagglutinin. Considerable variation was noted between donors in the phenotype and T-cell receptor (TCR) gamma gene rearrangements of CD4-8- -derived clones. In one donor, most clones remained CD4-8- and all were CD3+WT31- and therefore expressed gamma/delta heterodimers. TCR gamma gene rearrangements almost all involved C gamma 1. In contrast, most clones from a second donor were CD3+WT31+, and therefore expressed alpha/beta heterodimers, and many were positive for CD4 or CD8. Most clones from a third donor were CD3+WT31- with a high proportion of TCR gamma gene rearrangements involving C gamma 2. The V gamma 9JP rearrangement was exclusively confined to CD3+WT31- clones and was present in the majority of clones. Almost all CD3+WT31- clones showed TCR beta as well as gamma gene rearrangements. Most CD3+WT31- clones with at least one chromosome rearranged to C gamma 1 exhibited high non-major histocompatibility complex (MHC)-restricted cytotoxic activity, while most of those with two C gamma 2 rearrangements, and therefore expressing a non-disulphide-linked gamma/delta heterodimer, had low activity. Preincubation of effector cells with anti-CD3 strongly inhibited the cytotoxicity of CD3+WT31- clones while that of CD3+WT31+ clones was enhanced. This implicates the CD3-gamma/delta complex in target cell recognition by cytotoxic gamma/delta-bearing T-cell clones. The results show that there is heterogeneity between donors in the relative proportions of CD4-8- -derived clones expressing alpha/beta heterodimers and the different forms of the gamma/delta heterodimer.
Christmas
S E
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Department of Immunology, Paterson Institute for Cancer Research, Christie Hospital & Holt Radium Institute, Manchester, UK.
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D017252:CD3 Complex; D016827:CD8 Antigens; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell