title: Analysis of TNF-receptor and ligand superfamily molecules in patients with lymphoproliferative disease of granular lymphocytes.
abstract: In 21 patients with lymphoproliferative disease of granular lymphocytes (LDGL), we investigated the expression and the function of molecules belonging to TNF-receptor and TNF-ligand superfamilies (CD30/CD30L; CD40/CD40L; CD27/CD70; Fas [CD95]/FasL[CD95L]). Fourteen patients were characterized by a proliferation of granular lymphocytes (GLs) expressing the CD3(+)CD16(+) phenotype, whereas 7 cases showed the CD3(-)CD16(+) CD56 +/- phenotype. Our data show that both CD3(+) and CD3-GLs are preferentially equipped with CD30, CD40, CD40L, CD70, and CD95 antigens; this pattern is usually associated with the lack of CD27 and CD30L antigens expression. CD95L was demonstrated in the cytoplasm in 14 of 21 cases by flow cytometry, but a definite signal was demonstrated in all cases studied using polymerase chain reaction analysis. On functional grounds, a stimulatory activity on rIL-2 mediated redirected-cytotoxicity against Fcgamma+ P815 targets was demonstrated with anti-CD30, CD40, CD40L, CD70, CD95, and CD95L mAbs, although resting cells were unable to exhibit significant redirected-cell lysis. The addition of anti-CD30, CD30L, CD40, CD40L, CD95, and CD95L mAbs did not show any significant effect on cell proliferation at resting conditions or after rIL-2 stimulation, whereas anti-CD70 mAb mediated cell proliferation in 6 of 10 cases tested. This figure was not related to an increase in apoptotic cells, as investigated by Annexin-V expression. Our data indicate that both CD3(+) and CD3(-) GLs are equipped with different costimulatory antigens, supporting the concept that these cells are in vivo activated and suggesting that these molecules might play a role in the cytotoxic mechanisms of GLs. (Blood. 2000;96:647-654)
authors.affiliation: Division of Hematology, Vicenza Hospital, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Zambello
authors.forename: L
authors.initials: L
authors.lastname: Trentin
authors.forename: M
authors.initials: M
authors.lastname: Facco
authors.forename: M
authors.initials: M
authors.lastname: Siviero
authors.forename: S
authors.initials: S
authors.lastname: Galvan
authors.forename: F
authors.initials: F
authors.lastname: Piazza
authors.forename: A
authors.initials: A
authors.lastname: Perin
authors.forename: C
authors.initials: C
authors.lastname: Agostini
authors.forename: G
authors.initials: G
authors.lastname: Semenzato
mesh_terms: D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D017730:Ki-1 Antigen / Q000032:analysis; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008024:Ligands; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D019014:fas Receptor / Q000032:analysis
chemical_list: D017252:CD3 Complex; D019013:CD40 Antigens; D007376:Interleukin-2; D017730:Ki-1 Antigen; D008024:Ligands; D017452:Receptors, IgG; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor