B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4
Didier A. Mandelbrot, Mariette A. Oosterwegel, Koichi Shimizu, Akira Yamada, Gordon J. Freeman, Richard N. Mitchell, Mohammed H. Sayegh, Arlene H. Sharpe
Didier A. Mandelbrot, Mariette A. Oosterwegel, Koichi Shimizu, Akira Yamada, Gordon J. Freeman, Richard N. Mitchell, Mohammed H. Sayegh, Arlene H. Sharpe
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B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4

Abstract

To 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.

Authors

Didier A. Mandelbrot, Mariette A. Oosterwegel, Koichi Shimizu, Akira Yamada, Gordon J. Freeman, Richard N. Mitchell, Mohammed H. Sayegh, Arlene H. Sharpe

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T-cell activation in naive mice. Freshly isolated lymph node cells from ...
T-cell activation in naive mice. Freshly isolated lymph node cells from the indicated strains were stained for CD4 and CD69 and analyzed by flow cytometry. The percentages to the right of the dot plots are the proportion of CD4+ cells that are CD69+. This experiment is representative of five mice of each strain.