Large Granular Lymphocyte Proliferation: An Analysis of T-Cell Receptor Gene Arrangement and Expression and the Effect of In Vitro Culture With Inducing Agents

• Published in: Blood 1988-01, Vol.71 (1), p.52-58
• Main Authors: Chan, Wing C., Dahl, Carol, Waldmann, Thomas, Link, Susan, Mawle, Alison, Nicholson, Janet, Bach, Fritz H., Bongiovanni, Kathleen, McCue, Peter A., Winton, Elliott F.
• Format: Article
• Language: English
• Subjects: Acetamides - pharmacology; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Surface - analysis; Biological and medical sciences; Butyrates - pharmacology; Butyric Acid; CD3 Complex; Cell Differentiation - drug effects; Cells, Cultured; Cytotoxicity, Immunologic; Hematologic and hematopoietic diseases; Humans; Interleukin-2 - pharmacology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes - drug effects; Lymphocytes - immunology; Lymphocytes - ultrastructure; Lymphoproliferative Disorders - genetics; Lymphoproliferative Disorders - pathology; Medical sciences; Phenotype; Receptors, Antigen, T-Cell - genetics; Tretinoin - pharmacology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V71.1.52.52

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 Tαand complete Tβ gene transcripts were not detected, but a 1.0-kilobase Tβgene 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 Tγ gene rearrangement and CD3 δ chain expression; they are refractory to many induction signals in undergoing further T cell differentiation.