Human CD4^‐8^‐ ‐Derived Clones Phenotypic and Functional Characteristics and Variation between Donors in Patterns of T‐Cell Receptor y Gene Rearrangements

Abstract

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.

T‐Cell Receptor Gene Expression by Human γδ T‐Cell Clones from Peripheral Blood and Reproductive Tissues in Relation to Non‐MHC‐Restricted Cytotoxic Function

“…However, the most studied function in vitro is their non-MHC-restricted eytotoxic capacity following activation with interleukin 2 {IL-2). In some cases this can be inhibited by monoclonal antibodies to CD3 or the yd heterodimer [3,9,15], but in others only specific eytotoxieity is inhibited [28]. Other indirect evidenee that the receptor may participate in non-MHC-restricted eytotoxieity is the observation that most clones bearing tbe disulphide-linkcd form of the receptor are cytotoxic whereas most bearing the non-disulphide-linked form are not [9-11.…”