CD8+ T Cell Priming in Established Chronic Viral Infection Preferentially Directs Differentiation of Memory-like Cells for Sustained Immunity.
Immunity
; 49(4): 678-694.e5, 2018 10 16.
Article
in En
| MEDLINE
| ID: mdl-30314757
ABSTRACT
CD8+ T cell exhaustion impedes control of chronic viral infection; yet how new T cell responses are mounted during chronic infection is unclear. Unlike T cells primed at the onset of infection that rapidly differentiate into effectors and exhaust, we demonstrate that virus-specific CD8+ T cells primed after establishment of chronic LCMV infection preferentially generate memory-like transcription factor TCF1+ cells that were transcriptionally and proteomically distinct, less exhausted, and more responsive to immunotherapy. Mechanistically, adaptations of antigen-presenting cells and diminished T cell signaling intensity promoted differentiation of the memory-like subset at the expense of rapid effector cell differentiation, which was now highly dependent on IL-21-mediated CD4+ T cell help for its functional generation. Chronic viral infection similarly redirected de novo differentiation of tumor-specific CD8+ T cells, ultimately preventing cancer control. Thus, targeting these T cell stimulatory pathways could enable strategies to control chronic infection, tumors, and enhance immunotherapeutic efficacy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Differentiation
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CD8-Positive T-Lymphocytes
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Immunity
/
Immunologic Memory
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Lymphocytic Choriomeningitis
/
Lymphocytic choriomeningitis virus
Limits:
Animals
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2018
Document type:
Article