OX-40: life beyond the effector T cell stage.
Semin Immunol
; 10(6): 471-80, 1998 Dec.
Article
en En
| MEDLINE
| ID: mdl-9826580
The OX-40 receptor (OX-40R) is a transmembrane protein found on the surface of activated CD4(+) T cells. When engaged by an agonist such as anti-OX-40 antibody or the OX-40 ligand (OX-40L) during antigen presentation to T cell lines, the OX-40R generates a costimulatory signal that is as potent as CD28 costimulation. Engagement of OX-40R enhances effector and memory-effector T cell function by up-regulating IL-2 production and increasing the life-span of effector T cells. We hypothesize that the signal generated by the OX-40R inhibits activation-induced T cell death (AICD) and thereby increases the number of cells differentiating from the effector to memory T cell stage. In experimental autoimmune encephalomyelitis (EAE) OX-40R+ T cells are found only within the inflammatory site [central nervous system (CNS)]. Sorting OX-40R+ T cells from the CNS of animals with EAE revealed that they are autoantigen-specific T cells. Therefore, OX-40R-specific therapies were devised to eliminate or inhibit autoreactive T cells, while sparing the remainder of the T cell repertoire. In contrast, in vivo costimulation through the OX-40R in animals with cancer generated enhanced tumor-specific immunity leading to improved tumor-free survival. Thus, manipulation of the OX-40R during inflammatory responses can alter effector CD4(+) T cell function by enhancing or limiting T cell activation and survival.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glicoproteínas de Membrana
/
Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Semin Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
1998
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido