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

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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) γ gene rearrangements of CD4‐8‐ ‐derived clones. In one donor, most clones remained CD4‐8‐ and all were CD3+WT31‐ and therefore expressed γ/δ heterodimers. TCR γ gene rearrangements almost all involved Cγ1. In contrast, most clones from a second donor were CD3+WT31‐, and therefore expressed α/β heterodimers, and many were positive for CD4 or CD8. Most clones from a third donor were CD3+ WT31‐ with a high proportion of TCRγ gene rearrangements involving Cγ2. The Vγ9JP rearrangement was exclusively confined to CD3+WT31‐ clones and was present in the majority of clones. Almost all CD3+WT31‐ clones showed TCR β as well as γ gene rearrangements. Most CD3+WT31‐ clones with at least one chromosome rearranged to Cγ1 exhibited high non‐major histocompatibility complex (MHC)‐restricted cytotoxic activity, while most of those with two Cγ2 rearrangements, and therefore expressing a non‐disulphide‐linked γ/δ 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‐γ/δ complex in target cell recognition by cytotoxic γ/δ‐bearing T‐cell clones. The results show that there is heterogeneity between donors in the relative proportions of CD4‐8‐ ‐derived clones expressing α/β heterodimers and the different forms of the γ/δ heterodimer.

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