Analysis of TNF-receptor and ligand superfamily molecules in patients withlymphoproliferative disease of granular lymphocytes

Citation
R. Zambello et al., Analysis of TNF-receptor and ligand superfamily molecules in patients withlymphoproliferative disease of granular lymphocytes, BLOOD, 96(2), 2000, pp. 647-654
Citations number
42
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
00064971 → ACNP
Volume
96
Issue
2
Year of publication
2000
Pages
647 - 654
Database
ISI
SICI code
0006-4971(20000715)96:2<647:AOTALS>2.0.ZU;2-T
Abstract
In 21 patients with lymphoproliferative disease of granular lymphocytes (LD GL), 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 p roliferation of granular lymphocytes (GLs) expressing the CD3(+)CD16(+) phe notype, whereas 7 cases showed the CD3(-)CD16(+) CD56 +/- phenotype, Our da ta show that both CD3(+) and CD3-GLs are preferentially equipped with CD30, CD40, CD40L, CD70, and CD95 antigens; this pattern Is usually associated w ith 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 anal ysis. On functional grounds, a stimulatory activity on rIL-2 mediated redir ected-cytotoxicity against Fc gamma+ P815 targets was demonstrated with ant i-CD30, CD40, CD40L, CD70, CD95, and CD95L mAbs, although resting cells wer e unable to exhibit significant redirected-cell lysis. The addition of anti -CD30, CD30L, CD40, CD40L, CD95, and CD95L mAbs did not show any significan t effect on cell proliferation at resting conditions or after rIL-2 stimula tion, whereas anti-CD70 mAb mediated cell proliferation in 6 of 10 cases te sted. This figure was not related to an increase in apoptotic cells, as inv estigated by Annexin-V expression. Our data indicate that both CD3(+) and C D3(-) GLs are equipped with different costimulatory antigens, supporting th e concept that these cells are in vivo activated and suggesting that these molecules might play a role in the cytotoxic mechanisms of GLs, (C) 2000 by The American Society of Hematology.