G. Monastra et al., MEMBRANE FORM OF TNF-ALPHA INDUCES BOTH CELL-LYSIS AND APOPTOSIS IN SUSCEPTIBLE TARGET-CELLS, Cellular immunology, 171(1), 1996, pp. 102-110
Tumor necrosis factor alpha, in the secreted as well as membrane-assoc
iated (mTNF alpha) form, represents a cytotoxic effector mechanism of
activated macrophages; in contrast, direct evidence of the mTNF alpha
involvement in cytotoxic T lymphocyte (CTL)-mediated lysis has not yet
been obtained. We observed that following activation with anti-CD3 mo
noclonal antibody (mAb), both cloned CTL and peritoneal exudate lympho
cytes rapidly upregulated mTNF alpha; a similar effect was observed in
the macrophage cell line J774 after stimulation with lipopolysacchari
de endotoxin. Activated effector cells, which were fixed with paraform
aldehyde before testing, exerted lytic activity against the TNF-sensit
ive WEHI 164 tumor cell line, but not against the TNF-resistant P-815
mastocytoma. This effect was completely inhibited in the presence of a
nti-mouse TNF alpha Ab. Moreover, both mTNF alpha-expressing macrophag
es and CTL induced nuclear DNA fragmentation in WEHI 164 cells, which
was also blocked by anti-TNF alpha Ab and was accompanied by a morphol
ogic degeneration characteristic of the apoptotic form of cell death.
These data on the whole indicate a common mode of action for mTNF alph
a expressed on different cell populations endowed with cytotoxic capab
ility and also imply a role for this molecule in T-cell-mediated cytot
oxicity. (C) 1996 Academic Press, Inc.