Blood, 15 April 2002, Vol. 99, No. 8, pp. 2880-2889
IMMUNOBIOLOGY
B7-CTLA4 interaction promotes cognate destruction of tumor cells
by cytotoxic T lymphocytes in vivo
Xue-Feng Bai,
Jinqing Liu,
Kenneth F. May Jr,
Yong Guo,
Pan Zheng, and
Yang Liu
From the Department of Pathology and the Comprehensive
Cancer Center, Ohio State University Medical Center, Columbus.
Costimulatory molecules B7-1 and B7-2 (hereby collectively called
B7) interact with CD28 and CTLA4 on T cells and promote antitumor
immunity. The function of B7-CTLA4 interaction in antitumor CTL
response remains controversial. Here we used CD28
/ and
CD28+/ or CD28+/+ transgenic mice that
express the T-cell receptor specific for an unmutated tumor
antigen, P1A, and for tumor cells expressing a CTLA4-specific B7 mutant
to evaluate the function of CD28-B7 and CTLA4-B7 interactions in
induction and effector phases of antitumor immunity. We report that
B7-CD28 and B7-CTLA4 interactions promote tumor rejection. However,
this is achieved by distinct mechanisms. B7-CD28 interaction enhances
T-cell clonal expansion, though a role for this interaction in the
effector phase cannot be ruled out. In contrast, B7-CTLA4 interaction
enhances the CTL-mediated destruction of tumors, but not T-cell clonal expansion.
