MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4.
J Clin Invest
; 125(2): 699-714, 2015 Feb.
Article
en En
| MEDLINE
| ID: mdl-25607842
ABSTRACT
A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functional recovery following CNS injury; however, transfer of CD4+ T cells from wild-type mice, but not from IL-4-deficient mice, enhanced neuronal survival. Using a culture-based system, we determined that T cell-derived IL-4 protects and induces recovery of injured neurons by activation of neuronal IL-4 receptors, which potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these findings demonstrate that damage-associated molecules from the injured CNS induce a neuroprotective T cell response that is independent of MHCII/TCR interactions and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates neuroprotection and recovery of the injured CNS and suggest that strategies to enhance IL-4-producing CD4+ T cells have potential to attenuate axonal damage in the course of CNS injury in trauma, inflammation, or neurodegeneration.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Axones
/
Lesiones Encefálicas
/
Linfocitos T CD4-Positivos
/
Antígenos de Histocompatibilidad Clase II
/
Interleucina-4
/
Enfermedades Neurodegenerativas
/
Sistema de Señalización de MAP Quinasas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Clin Invest
Año:
2015
Tipo del documento:
Article