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

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.