TCR-pMHC encounter differentially regulates transcriptomes of tissue-resident CD8 T cells.
Akihiro YoshizawaKevin BiDerin B KeskinGuanglan ZhangBruce ReinholdEllis L ReinherzPublished in: European journal of immunology (2017)
To investigate the role of TCR-pMHC interaction in regulating lung CD8 tissue-resident T cell (TR ) differentiation, polyclonal responses were compared against NP366-374 /Db and PA224-233 /Db , two immunodominant epitopes that arise during influenza A infection in mice. Memory niches distinct from iBALTs develop within the lamina propria, supporting CD103+ and CD103- CD8 TR generation and intraepithelial translocation. Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) identify dominant TCR, adherens junction, RIG-I-like and NOD-like pattern recognition receptor as well as TGF-β signaling pathways and memory signatures among PA224-233 /Db T cells consistent with T resident memory (TRM ) status. In contrast, NP366-374 /Db T cells exhibit enrichment of effector signatures, upregulating pro-inflammatory mediators even among TRM . While NP366-374 /Db T cells manifest transcripts linked to canonical exhaustion pathways, PA224-233 /Db T cells exploit P2rx7 purinoreceptor attenuation. The NP366-374 /Db CD103+ subset expresses the antimicrobial lactotransferrin whereas PA224-233 /Db CD103+ utilizes pore-forming mpeg-1, with <22% of genes correspondingly upregulated in CD103+ (or CD103- ) subsets of both specificities. Thus, TCR-pMHC interactions among TR and antigen presenting cells in a tissue milieu strongly impact CD8 T cell biology.
Keyphrases
- regulatory t cells
- genome wide
- network analysis
- magnetic resonance
- working memory
- signaling pathway
- patient safety
- type diabetes
- induced apoptosis
- poor prognosis
- gene expression
- quality improvement
- metabolic syndrome
- high grade
- cell proliferation
- copy number
- case report
- single cell
- oxidative stress
- computed tomography
- insulin resistance
- dna methylation
- pi k akt
- peripheral blood
- endoplasmic reticulum stress
- data analysis