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J. Exp. Med.,
Volume 189, Number 7, April 5, 1999 1157-1162
By
From the Malaghan Institute of Medical Research, Wellington School of Medicine, Wellington,
New Zealand
The mechanisms that regulate the strength and duration of CD8+ cytotoxic T cell activity
determine the effectiveness of an antitumor immune response. To better understand the antitumor effects of anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody treatment, we analyzed the effect of CTLA-4 signaling on CD8+ T cells in vitro and in vivo. In
vitro, cross-linking of CTLA-4 on purified CD8+ T cells caused decreased proliferative responses
to anti-CD3 stimulation and rapid loss of activation marker expression. In vivo, blockade of
CTLA-4 by neutralizing anti-CTLA-4 mAb greatly enhanced the accumulation, activation,
and cytotoxic activity of CD8+ T cells induced by immunization with Ag on dendritic cells
(DC). This enhanced response did not require the expression of MHC class II molecules on
DC or the presence of CD4+ T cells. These results demonstrate that CTLA-4 blockade is able to
directly enhance the proliferation and activation of specific CD8+ T cells, indicating its potential
for tumor immunotherapy even in situations in which CD4+ T cell help is limited or absent.
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