Acute Traumatic Brain Injury Induces CD4+ and CD8+ T Cell Functional Impairment by Upregulating the Expression of PD-1 via the Activated Sympathetic Nervous System.
Neuroimmunomodulation
; 26(1): 43-57, 2019.
Article
en En
| MEDLINE
| ID: mdl-30695785
ABSTRACT
OBJECTIVE:
Traumatic brain injury (TBI) induces immunosuppression in the acute phase, and the activation of the sympathetic nervous system (SNS) might play a role in this process, but the mechanism involved is unknown. Herein, we explored the impact of acute (a)TBI on the peripheral immune system and its correlation with the SNS and the T cell exhaustion marker, PD-1 (programmed cell death-1).METHODS:
Flow cytometry (FCM) was performed to analyze the expression of T cell markers and intracellular cytokines, interferon-γ and tumor necrosis factor-α, and the T cell exhaustion marker, PD-1, in the peripheral blood mononuclear cells (PBMCs) of TBI rats. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the concentration of norepinephrine (NE) in the serum. Propranolol was administrated to block the SNS in vivo and NE stimulation was used to imitate the activation of the SNS in vitro.RESULTS:
We found that the concentration of NE was significantly elevated after TBI, and the dysfunction of CD4+ and CD8+ T cells was reversed by the SNS blocker propranolol in vivo and imitated by the SNS neurotransmitter NE in vitro. The expression of PD-1 on CD4+ and CD8+ T cells was upregulated after aTBI, which was reversed by propranolol administration in vivo and imitated by NE stimulation in vitro. Furthermore, the PD-1 blocker reversed the dysfunction of CD4+ and CD8+T cells in vitro.CONCLUSION:
Our findings demonstrated that aTBI activated the SNS, and further upregulated the expression of PD-1 on CD4+ and CD8+ T cells, which, in turn, impaired their function and contributed to immunosuppression.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sistema Nervioso Simpático
/
Linfocitos T CD4-Positivos
/
Norepinefrina
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Linfocitos T CD8-positivos
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Receptor de Muerte Celular Programada 1
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Contusión Encefálica
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Tolerancia Inmunológica
Límite:
Animals
Idioma:
En
Revista:
Neuroimmunomodulation
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
NEUROLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China