Large granular lymphocyte proliferation: an analysis of T-cell receptor
gene arrangement and expression and the effect of in vitro culture with
inducing agents
WC Chan, C Dahl, T Waldmann, S Link, A Mawle, J Nicholson, FH Bach, K Bongiovanni, PA McCue and EF Winton
Department of Pathology and Laboratory Medicine, Emory University School of
Medicine, Atlanta, GA.
The status of the T cell receptor beta and gamma 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 alpha and complete T beta gene transcripts were not detected, but a
1.0-kilobase T beta 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 delta 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
greater than or equal to 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 gamma gene
rearrangement and CD3 delta chain expression; they are refractory to many
induction signals in undergoing further T cell differentiation.
Volume 71,
Issue 1,
pp. 52-58,
01/01/1988
Copyright © 1988 by The American Society of Hematology