Long peptide vaccination can lead to lethality through CD4+ T cell-mediated cytokine storm.
J Immunol
; 185(2): 892-901, 2010 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-20543102
ABSTRACT
The optimization of anticancer therapeutic vaccines can lead to better efficacy but also to stronger adverse effects. In a mouse model of antitumor vaccination using a long peptide (LP), which included MHC class I- and II-restricted male (H-Y) epitopes, we observed unexpected mortality. Mice with an increased frequency of anti-H-Y CD4 T cells were primed with LP+CpG and boosted 10 d later. Within hours of boost, they displayed shock-like signs with high mortality. Serum cytokine levels were high. TNF-alpha secreted by the CD4 T cells was identified as the key effector molecule. Priming with a short peptide (SP), which included the MHC class II-restricted epitope, was a more efficient primer than LP, but did not lead to mortality when used as boost. The high mortality induced by LP compared with SP was probably related to its specific ability to be presented by B cells. Finally, targeting the LP sequence to dendritic cells allowed tumor protection without side effects. Our data 1) confirm that the immune system can be very dangerous; 2) caution against the use of systemic activation of high-frequency Ag-specific T cells as induced by high doses of LP; and 3) underline the benefit of targeting Ag to dendritic cells.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T CD4-Positivos
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Citocinas
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Vacunas contra el Cáncer
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Vacunas de Subunidad
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Francia