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. |