T-cell intrinsic effects of GITR and 4-1BB during viral infection and cancer immunotherapy.
Immunol Rev
; 244(1): 197-217, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-22017440
ABSTRACT
GITR [glucocorticoid inducible tumor necrosis factor receptor (TNFR)-related protein] and 4-1BB are costimulatory TNFR family members that are expressed on regulatory and effector T cells as well as on other cells of the immune system. Here we discuss the role of GITR and 4-1BB on T cells during viral infections and in cancer immunotherapy. Systemic treatment with agonistic anti-4-1BB antibody leads to a number of immune system abnormalities, and clinical trials of anti-4-1BB have been terminated. However, other modes of 4-1BB ligation may be less toxic. To date, similar toxicities have not been reported for anti-GITR treatment of mice, although anti-GITR antibodies can exacerbate mouse autoimmune models. Intrinsic effects of GITR and 4-1BB on effector T cells appear to predominate over their effects on other cell types in some models. Despite their similarities in enhancing T-cell survival, 4-1BB and GITR are clearly not redundant, and both pathways are required for maximal CD8(+) T-cell responses and mouse survival following severe respiratory influenza infection. GITR uses TNFR-associated factor (TRAF) 2 and TRAF5, whereas 4-1BB recruits TRAF1 and TRAF2 to mediate survival signaling in T cells. The differential use of signaling adapters combined with their differential expression may explain the non-redundant roles of GITR and 4-1BB in the immune system.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Transdução de Sinais
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Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral
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Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral
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Proteína Relacionada a TNFR Induzida por Glucocorticoide
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Imunidade Inata
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Anticorpos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Immunol Rev
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Canadá