Human xenospecific T suppressor cells inhibit T helper cell proliferation to porcine aortic endothelial cells, and NF-kappaB activity in porcine APC.
Human T suppressor cells (Ts), capable of preventing autologous T helper cells (Th) from reacting against xenogeneic pig endothelial cells and pig APC can be generated in vitro. Ts derive from a population of CD3(+)CD8(+)CD28(-) T lymphocytes and specifically recognize the MHC class I antigens of the APC used for in vitro immunization. To study the mechanism that underlies suppression, we investigated whether Ts inhibit the expression of costimulatory molecules in xenogeneic professional and semiprofessional APC. We found that Ts down-regulate Th-induced expression of CD86 in pig APC, and that this effect occurs at the level of transcription, as indicated by nuclear run-on and Northern blot assays. EMSA results revealed that inhibition of CD86 expression is mediated by inactivation of transcription factor NF-kappaB. Furthermore, transfection of pig APC with a vector expressing NF-kappaB p65 partially rescued Th-induced expression of the CD86 molecule. These results strongly support the concept that xenospecific Ts inhibit the APC function of xenogeneic cells by preventing activation of NF-kappaB.
Ciubotariu
R
R
Department of Pathology, College of Physicians & Surgeons of Columbia University, New York, NY 10032, USA.
Li
J
J
Colovai
A I
AI
Platt
J L
JL
Cortesini
R
R
Suciu Foca Cortesini
N
N
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D001011:Aorta; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D002455:Cell Division; D017690:Cell Transplantation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013552:Swine; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014158:Transcription, Genetic; D014181:Transplantation Immunology / Q000276:immunology*; D014183:Transplantation, Heterologous; D015854:Up-Regulation
D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D023201:CD40 Ligand