T-cell activation by the CD28 ligand B7 is required for cardiac allograft rejection in vivo.
Organ graft rejection is a T-cell-dependent process. The activation of alloreactive T cells requires stimulation of the T-cell receptor/CD3 complex by foreign major histocompatibility complex (MHC)-encoded gene products. However, accumulating evidence suggests that, in addition to T-cell receptor occupancy, other costimulatory signals are required to induce T-cell activation. Previously, the CD28 receptor expressed on T cells has been shown to serve as a surface component of a signal transduction pathway that can provide costimulation. In vitro, interaction of CD28 with its natural ligand B7 expressed on the surface of activated B cells or macrophages can act as a costimulus to induce proliferation and lymphokine production in antigen receptor-activated T cells. We now report evidence that stimulation of T cells by the CD28 ligand B7 is a required costimulatory event for the rejection of a MHC-incompatible cardiac allograft in vivo. These results demonstrate that the B7/CD28 activation pathway plays an important role in regulating in vivo T-cell responses.
Turka
L A
LA
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0650.
Linsley
P S
PS
Lin
H
H
Brady
W
W
Leiden
J M
JM
Wei
R Q
RQ
Gibson
M L
ML
Zheng
X G
XG
Myrdal
S
S
Gordon
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018106:CD28 Antigens; D002478:Cells, Cultured; D006084:Graft Rejection; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D008024:Ligands; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013934:Thymectomy; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface