International Immunology, Vol 9, 1271-1279, Copyright © 1997 by Oxford University Press
A Poggi, E Tomasello, V Revello, L Nanni, P Costa and L Moretta
p40 was previously described as a regulatory molecule capable of inhibiting
both the natural and the CD16-mediated cytotoxicity of NK cells. In this
study, we analyze the effect of p40 molecule engagement on the NK cell
triggering induced by activating HLA class I-specific NK receptors (NKR) or
on TCR alpha beta-mediated T cell activation. CD3- CD16+ NK cell clones
expressing activating NKR (either CD94 or p50) were analyzed in a
redirected killing assay using P815 target cells and appropriate mAb. A
strong target cell lysis was detected in the presence of anti-NKR or
anti-CD16 mAb alone. Addition of anti-p40 mAb resulted in a strong
inhibition of both anti-NKR or anti-CD16 mAb- induced cytolysis. mAb
specific for either CD45 or lymphocyte function associated antigen-1 did
not exert any inhibitory effect in the same experimental system. Free
intracellular calcium ([Ca2+]i) increase induced by mAb cross-linking of
activating CD94 or p50 was inhibited by simultaneous engagement of p40
molecules, but not of other NK surface molecules including CD44 and CD56.
In addition, cross-linking of p40 molecules strongly inhibited the
CD94-induced tumor necrosis factor- alpha and IFN-gamma production.
Analysis of TCR alpha beta or gamma delta T cell clones revealed that the
engagement of p40 molecules, using specific mAb, induced some degree of
inhibition only on anti-V beta (but not anti-V delta or anti-CD3)
mAb-induced cytotoxicity. On the other hand, the p40 molecule engagement
prevented T cell proliferation induced by either anti-V beta 8 or anti-V
delta 2 mAb. A similar inhibitory effect was found on the IL-2-induced NK
cell proliferation. Taken together, our present findings suggest that p40
may play a role in the regulation of NK and T lymphocyte activation and
proliferation.
ARTICLES
p40 molecule regulates NK cell activation mediated by NK receptors for HLA class I antigens and TCR-mediated triggering of T lymphocytes
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
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