T cell receptor δ gene organization and expression in normal and leukemic natural killer cells

In peripheral blood most NK activity is by CD3^- cells with large granular lymphocyte morphology which cannot be assigned to a specific hemopoietic lineage. In accordance with previous studies we have analyzed the organization of the TCR δ gene, which rearranges early in thymic ontogeny, in normal NK cells, and in granular lymphocytes proliferative disorders (GLPD), in an effort to further define their relationship to the T cell differentiation pathway and to identify a possible marker of clonality for CD3^- GLPD. The α/δ locus was rearranged in five cases of CD3⁺ GLPD with a biallelic deletion of the Cδ region, suggesting V-J α rearrangement, whereas CD3^- GLPD and normal CD3^- NK cells had the δ gene in germ-line configuration, but suprisingly expressed high levels of TCR δ-related mRNA. On the basis of this finding and of the presence of truncated TCR-β and CD3-ε mRNA, we are led to speculate on a possible ontogenic relationship of NK cells to the T cell differentiation pathway at stages preceding TCR gene rearrangement.