T cell receptor (α, β, γ) gene rearrangements and expression in normal and leukemic large granular lymphocytes/natural killer cells

The large granular lymphocyte (LGL) population, which effects a natural killer (NK) function, consists of cells whose lineage derivation has not been clearly established on the basis of phenotypic and functional properties. To clarify the relationship of LGL/NK cells to T cells we studied patterns of rearrangement and expression of the T cell receptor (Ti) genes α, β, and γ in normal human LGLs; in CD8⁺, CD8^-, Mol⁺, and Mol^- LGL subsets; and in 17 cases of leukemic LGL proliferations (TγLPD). T(α), T(β), and T(γ) genes were not expressed, nor were T(β) and T(γ) genes rearranged in normal LGLs or LGL subsets. The TγLPD were divided into two groups. One group (15/17 cases) was characterized as CD3⁺ and displayed Ti gene rearrangements. Seven of these cases were reactive with monoclonal antibody WT31, which suggested expression of an α/β heterodimer on the cell surface. The other group (2/17 cases) was CD3^- with unrearranged Ti genes. These results indicate that the normal LGL/NK population is homogeneous and distinct from the normal T cell population because it does not express, and as a result, cannot effect its immune function through the T cell receptor molecules. Conversely, TγLPDs represent a heterogeneous group of lymphoproliferative diseases within which the CD3^-, Ti^- cases most likely represent the neoplastic counterpart of normal LGL cells. The more frequent CD3⁺ cases may be related to recently described NK-like T cells. The observations that normal LGLs maintain germline Tγ genes and that many CD3⁺ TγLPD display an α/β heterodimer suggest that a Tγ-containing receptor may not be necessary for NK or NK-like cytotoxicity.