International Immunology, Vol 10, 1733-1740, Copyright © 1998 by Oxford University Press
J She, K Matsui, C Terhorst and ST Ju
Activation-induced cell death (AICD) occurs primarily in recently activated
T cells after a second TCR triggering. Since a threshold in the activation
status may be critical for AICD, it is likely that the CD3 ITAM, docking
sites for tyrosine kinases, regulate AICD. A 'threshold model' for AICD was
tested by using two targeted mutant mouse strains lacking either the zeta
chain (CD3zeta-/-) or the ITAM of the zeta chain
(CD3zeta-/-:Tgzetadelta67-150). Although the T cells from the CD3zeta-/-
mice express extremely low levels of surface TCR, a subpopulation
(approximately 18%) of activated T cells could be induced to express
TCR/FcepsilonRI gamma by using a powerful polyclonal activation protocol.
These activated TCR/FcRI gamma T cells were capable of undergoing AICD, but
its induction required 10 times as much anti-CD3epsilon mAb as that
required for AICD of wild-type T cells. Thus, the intensity of AICD
correlated with the level of CD3 expression and was less efficient with
activated, CD3zeta(-/-)-derived T cells. By contrast, AICD of T cells from
the CD3zeta-/-:Tgzetadelta67-150 mice could be induced with low doses of
anti-CD3epsilon mAb and the extent of AICD was comparable to T cells from
wild-type mice. The AICD induced in T cells from CD3-/-,
CD3zeta-/-:Tgzetadelta67-150 and normal controls was specifically inhibited
by Fas-Ig fusion proteins. Our data support the 'threshold model' of AICD
by demonstrating that AICD is controlled by the strength of T cell
activation.
ARTICLES
Activation-induced apoptosis of mature T cells is dependent upon the level of surface TCR but not on the presence of the CD3 zeta ITAM
Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
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