Inhibition of IL-2 or NF-κB Subunit c-Rel-Dependent Signaling Inhibits Expansion of Regulatory T Cells During Acute Friend Retrovirus Infection.
Viral Immunol
; 33(5): 353-360, 2020 06.
Article
en En
| MEDLINE
| ID: mdl-32315584
ABSTRACT
In retroviral infections, different immunological mechanisms are involved in the development of a chronic infection. In the Friend virus (FV) model, regulatory T cells (Tregs) were found to induce CD8+ T cell dysfunction before viral clearance is achieved and thus contribute to viral chronicity. Although studied for decades, the exact suppressive mechanisms of Tregs in the FV model remain elusive and an unavailable therapeutic target. However, extracellular IL-2 and intracellular NF-κB signaling were shown to be important pathways for Treg expansion and activation. Therefore, we decided to focus on these two pathways to test therapeutic approaches inhibiting Treg activation during FV infection. In this study, we show that the inhibition of either IL-2 or the NF-κB subunit c-Rel, impaired Treg expansion and activation at 2 weeks post-FV infection. Total numbers of Tregs as well as activated Tregs were reduced in FV-infected mice after treatment with anti-IL-2 antibodies or the c-Rel blocking reagent pentoxifylline. Surprisingly, this did not affect the expansion or function of virus-specific CD8+ T cells nor viral loads in the spleen. However, our data suggest that neutralization of IL-2 as well as blocking c-Rel efficiently inhibits virus-induced Treg expansion.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Transducción de Señal
/
Interleucina-2
/
Linfocitos T Reguladores
/
Infecciones por Retroviridae
/
Proteínas Proto-Oncogénicas c-rel
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Viral Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
VIROLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania