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
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.