Infection-induced type I interferons critically modulate the homeostasis and function of CD8+ naïve T cells.
Nat Commun
; 12(1): 5303, 2021 09 06.
Article
em En
| MEDLINE
| ID: mdl-34489451
ABSTRACT
Naïve T (Tn) cells require two homeostatic signals for long-term survival tonic T cell receptorself-peptide-MHC contact and IL-7 stimulation. However, how microbial exposure impacts Tn homeostasis is still unclear. Here we show that infections can lead to the expansion of a subpopulation of long-lived, Ly6C+ CD8+ Tn cells with accelerated effector function. Mechanistically, mono-infection with West Nile virus transiently, and polymicrobial exposure persistently, enhances Ly6C expression selectively on CD5hiCD8+ cells, which in the case of polyinfection translates into a numerical CD8+ Tn cell increase in the lymph nodes. This conversion and expansion of Ly6C+ Tn cells depends on IFN-I, which upregulates MHC class I expression and enhances tonic TCR signaling in differentiating Tn cells. Moreover, for Ly6C+CD8+ Tn cells, IFN-I-mediated signals optimize their homing to secondary sites, extend their lifespan, and enhance their effector differentiation and antibacterial function, particularly for low-affinity clones. Our results thus uncover significant regulation of Tn homeostasis and function via infection-driven IFN-I, with potential implications for immunotherapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Febre do Nilo Ocidental
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Antígenos Ly
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Interferon gama
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Interferon-alfa
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Linfócitos T CD8-Positivos
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Homeostase
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Memória Imunológica
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2021
Tipo de documento:
Article