Innateness transcriptome gradients characterize mouse T lymphocyte populations.

Area of Science:

• Immunology
• Cell Biology
• Genomics

Background:

• Lymphocytes are broadly classified into adaptive (T and B cells) and innate types, distinguished by response speed and antigen recognition.
• Some T cell populations exhibit intermediate characteristics, capable of rapid responses via T cell receptor (TCR) or cytokine stimulation.

Purpose of the Study:

• To define a gradient of innate gene expression in mouse innate-like T cells.
• To investigate the applicability of this gradient to other mouse T lymphoid populations.
• To characterize the chromatin landscape and activation pathways associated with innate-like T cells.

Main Methods:

• Linear mixed models were constructed using publicly available datasets.
• ATAC-seq (assay for transposase-accessible chromatin using sequencing) data was analyzed to assess chromatin landscape.
• Gene expression patterns and downstream signaling proteins were examined.

Main Results:

• A gradient of innate gene expression was identified in mouse innate-like T cells, applicable to other T lymphoid populations.
• A similar gradient was observed in the chromatin landscape.
• Higher innate scores correlated with increased innate immune response transcripts and antigen experience evidence.
• The innate gene program was distinct from T helper 1, T helper 2, and T helper 17 responses.
• Innate-like T cells showed reduced calcium-dependent TCR-mediated activation compared to naive CD4 and CD8 T cells.

Conclusions:

• Mouse innate-like T cell populations share common gene expression programs and activation pathways.
• These pathways differ from those of naive CD4 and CD8 T cells.
• A spectrum of T cell responses exists, bridging innate and adaptive immunity.