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Publication : B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4.

First Author  Mandelbrot DA Year  2001
Journal  J Clin Invest Volume  107
Issue  7 Pages  881-7
PubMed ID  11285307 Mgi Jnum  J:68642
Mgi Id  MGI:1933013 Doi  10.1172/JCI11710
Citation  Mandelbrot DA, et al. (2001) B7-dependent T-cell costimulation in mice lacking CD28 and CTLA4. J Clin Invest 107(7):881-7
abstractText  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.
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