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 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.
D000081:Acetamides / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D000954:Antigens, Surface / Q000032:analysis; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D017252:CD3 Complex; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure*; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology
D000081:Acetamides; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D002087:Butyrates; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D020148:Butyric Acid; D014212:Tretinoin; C014026:hexamethylene bisacetamide