Large granular lymphocyte proliferation: An analysis of T-cell receptor gene arrangement and expression and the effect of in vitro culture with inducing agents

The status of the T cell receptor β and γ genes in natural killer (NK) cells was investigated in two patients with a marked expansion of CD2+, CD3- NK cells. Both genes were found to be in the germline state. The T(α) and complete T(β) gene transcripts were not detected, but a 1.0-kilobaste T(β) gene transcript could be demonstrated at low levels in freshly isolated cells and at a much higher level in interleukin-2 (IL-2)-cultured cells. The transcript coding for the δ chain of the CD3 complex was also absent. These cells were cultured in IL-2 with or without the addition of the differentiation-inducing agents: retinoic acid, N,N-hexamethylene bisacetamide, and sodium butyrate. The cultured cells retained their NK activity except in culture with sodium butyrate at ≥1 mmol/L. Expression of CD3 or other T cell surface markers by the NK cells was not observed in these cultures. Either CD2+, CD3- NK cells are derived from a non-T lineage, or they have diverged from the T cell lineage earlier than the stage of T(γ) gene rearrangement and CD3 δ chain expression; they are refractory to many induction signals in undergoing further T cell differentiation.