Year: 2001
Type: article
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.
DOI: 10.1172/jci11710
Authors: Didier A. Mandelbrot, Mariette A. Oosterwegel, Koichi Shimizu, Akira Yamada, Gordon J. Freeman, Richard N. Mitchell, Mohammed H. Sayegh, Arlene H. Sharpe
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Awards: G1320150131, G1638398978, G1826378132, G204514443, In Vivo Function of the B7 Family of Costimulators, Costimulation and Cytokines in Tolerance, PATHOGENESIS OF TRANSPLANT ASSOCIATED ARTERIOSCLEROSIS, G368152584, G4736635489, ANTITUMOR AND COSTIMULATORY ACTIVITY OF B7 ON T CELLS, INDUCTION OF HOST-SPECIFIC TOLERANCE IN ALLOGENIC BMT, G7290072735, G8601752015, INTRATHYMIC TRANSPLANTATION TOLERANCE BY MHC PEPTIDES, G9000057796, Costimulatory Mechanisms of Autoimmunity
OpenAlex ID: W2041980736