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Blood, Vol. 96 No. 2 (July 15), 2000:
pp. 647-654
Analysis of TNF-receptor and ligand superfamily molecules in
patients with lymphoproliferative disease of granular lymphocytes
Renato Zambello,
Livio Trentin,
Monica Facco,
Marta Siviero,
Silvia Galvan,
Francesco Piazza,
Alessandra Perin,
Carlo Agostini, and
Gianpietro Semenzato
From the Division of Hematology, Vicenza Hospital, Vicenza; and
Padova University School of Medicine, Department of Clinical and
Experimental Medicine, Clinical Immunology Branch, Padova, Italy.
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 Fc + 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.
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