Phenotypic diversity of natural killer (NK) populations in patients with NK-type lymphoproliferative disease of granular lymphocytes.
Using monoclonal antibodies (MoAbs) termed GL183 and EB6, directed to a novel family of natural killer (NK) specific triggering molecules, four functional subsets of NK cells have been recently defined (GL183+EB6-; GL183+EB6+; GL183-EB6+; GL183-EB6-). In healthy individuals, all these subsets are represented in variable portion. The expression of EB6 and GL183 surface antigens has been analyzed in a series of 14 patients with lymphoproliferative disease of granular lymphocytes (LDGL) characterized by a chronic CD3-CD16+ lymphocytosis. Our data showed that in 11 of 14 cases, the proliferation was specifically sustained by one of the four possible subsets of granular lymphocytes (GLs) (seven cases: EB6-GL183-; three cases: EB6+GL183-; one case: EB6-GL183+). In the remaining three cases, a pattern was demonstrated that is consistent with that of healthy individuals (ie, the presence of all four subsets). When expressed on GL surfaces, in the majority of cases tested both EB6 and GL183 MoAbs behave as functional surface molecules as assessed in the redirected killing of P815 target cells. We also provided evidence that EB6+GL183+ proliferating cells show a definite (type 1) in vitro NK specificity as do their normal counterparts. The unique expansion of a defined subset of NK cells in most patients with LDGL suggests that the pathologic noxa leading to GL proliferation selectively acts on a specific subset of NK lymphocytes.
Zambello
R
R
Istituto di Medicina Clinica, Università di Padova, Italy.
Trentin
L
L
Ciccone
E
E
Bulian
P
P
Agostini
C
C
Moretta
A
A
Moretta
L
L
Semenzato
G
G
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D017452:Receptors, IgG