International Immunology, Vol 9, 935-944, Copyright © 1997 by Oxford University Press
JG Chai and RI Lechler
The induction of non-responsiveness in resting murine CD4+ T cells was
investigated using immobilized anti-CD3 mAb. Incubation of freshly isolated
CD4+ T cells with immobilized anti-CD3 mAb led to apoptosis in 40-60%
cells. The surviving cells were profoundly non-responsive to subsequent
mitogenic stimulation. The non-responsive state was characterized by a lack
of IL-2 production and hyper-responsiveness to added IL-2, but was not
explained by further activation-induced cell death. The induction of
non-responsiveness was not due to modulation of the TCR-CD3 complex, and
required partial activation of the T cells in that it was accompanied by an
increase in cell size and was inhibited by addition of cyclosporin A.
Finally, analysis of anti-CD3-mediated responses in naive and memory CD4+ T
cells, separated on the basis of CD44 expression, showed that both naive
and memory T cells have similar sensitivity to immobilized anti-CD3
mAb-induced activation, apoptosis and anergy. These results demonstrate
that TCR-CD3 engagement on freshly isolated resting CD4+ naive and memory T
cells, In the absence of co-stimulation, as achieved by plastic-immobilized
anti-CD3 mAb, induces both anergy and cell death.
ARTICLES
Immobilized anti-CD3 mAb induces anergy in murine naive and memory CD4+ T cells in vitro
Department of Immunology, Royal Postgraduate Medical School, London, UK.
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