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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


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  Copyright © 1988 by American Society of Hematology         Online ISSN: 1528-0020