Methods for inducing T cell tolerance to tissue or organ graft

• Main Authors: F. H. DURIE, D. C. PARKER, R. J. NOELLE
• Format: Patent
• Language: Chinese; English
• Published: 14.01.2004
• Edition: 7
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROCESSES USING MICROORGANISMS; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

一种在移植接受体中诱导对组织或器官移植物的T细胞耐受的方法被揭示。该法包括给予受实验者1)同种的或异种的细胞，这些细胞可表达供体抗原，并在其表面有一种配体，此配体可同接受体T细胞表面上的介导接触依赖性辅助效应物功能的受体相互作用；和2)一种能抑制配体同受体相互作用的受体的拮抗剂。在一个优选实施方案中，同种或异种细胞是B细胞，优选静止期B细胞，T细胞表面的介导接触依赖性辅助效应物功能的分子是gp39。优选的gp39的拮抗剂是抗-gp39抗体。同种细胞或异种细胞和gp39拮抗剂典型的是在组织或器官移植前施用于移植接受体。本发明中的方法可用来诱导对诸如下列移植物的T细胞耐受：肝、肾、心脏、肺、皮肤、肌肉、神经组织、胃和肠。一种用来治疗糖尿病的方法也被揭示，该法包括给予受实验者以能表达供体抗原的同种或异种细胞，gp39的拮抗剂及胰岛。 Methods for inducing T cell tolerance to a tissue or organ graft in a transplant recipient are disclosed. The methods involve administering to a subject: 1) an allogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ. The methods of the invention can be used to induce T cell tolerance to transplants such as liver, kidney, heart, lung, skin, muscle, neuronal tissue, stomach and intestine. A method for treating diabetes comprising administering to a subject allogeneic or xenogeneic cells expressing donor antigens, a gp39 antagonist and pancreatic islets is also disclosed.