Didier A. Mandelbrot, Mariette A. Oosterwegel, Koichi Shimizu, Akira Yamada, Gordon J. Freeman, Richard N. Mitchell, Mohammed H. Sayegh, Arlene H. Sharpe
J Clin Invest. 2001;
107(7):881
doi:10.1172/JCI11710
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o examine whether B7 costimulation can be mediated by a molecule on T cells that is neither CD28 nor CTLA4, we generated mice lacking both of these receptors. CD28/CTLA4–/– mice resemble CD28–/– mice in having decreased expression of T-cell activation markers in vivo and decreased T-cell proliferation in vitro, as compared with wild-type mice. Using multiple approaches, we find B7-dependent costimulation in CD28/CTLA4–/– mice. The proliferation of CD28/CTLA4–/– T cells is inhibited by CTLA4-Ig and by the use of antigen-presenting cells lacking both B7-1 and B7-2. CD28/CTLA4–/– T-cell proliferation is increased by exposure to Chinese hamster ovary cells transfected with B7-1 or B7-2. Finally, administration of CTLA4-Ig to CD28/CTLA4–/– cardiac allograft recipients significantly prolongs graft survival. These data support the existence of an additional receptor for B7 molecules that is neither CD28 nor CTLA4.
