B7(+)-transfectant tubular epithelial cells induce T cell anergy, ignorance or proliferation.
We have previously established that interferon (IFN)-gamma stimulated, antigen-pulsed tubular epithelial cells (TEC) stimulate antigen (Ag) specific activation of T cell hybridomas to express IL-2. In contrast, these Ag pulsed TEC do not stimulate T helper 1 (Th1) clones to proliferate, but rather render them unresponsive, since Ag pulsed spleen cells cannot restore these cells to proliferate. The interaction of the T cell CD28 surface protein with its ligand B7 expressed on Ag presenting cells bearing Ia is a potent co-stimulatory signal capable of inducing T cell proliferation. Hence, the lack of B7 on TEC was hypothesized to be responsible for anergy in these Th1 cells. Therefore, the B7 gene was transfected into a SV40 transformed TEC or Chinese hamster ovary (CHO) cells, and created TEC and CHO cells expressing surface B7 protein. TEC-B7 (IFN-gamma stimulated, Ag pulsed) express Ia and induce IL-2 production by T cell hybridomas. In contrast, T cell proliferation was not induced by TEC-B7 or CHO-B7 cells; however, these Th1 cells were not anergic since they could be stimulated to proliferate to Ag pulsed spleen cells (immunological ignorance). However, co-cultivating TEC- B7 (IFN-gamma stimulated, Ag pulsed) with Th1 cells stimulated through the T cell receptor (TCR) using anti-CD3 monoclonal antibody (mAb) caused these Th1 cells to proliferate. Furthermore, anti-CD28 and anti-B7 mAbs blocked this response.(ABSTRACT TRUNCATED AT 250 WORDS)
Yokoyama
H
H
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Zheng
X
X
Strom
T B
TB
Kelley
V R
VR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D002460:Cell Line; D017635:Clonal Anergy / Q000276:immunology*; D004848:Epithelium / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007687:Kidney Tubules, Proximal / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D000949:Histocompatibility Antigens Class II; D008024:Ligands