Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells

Area of Science:

• Immunology
• Transcriptomics
• Human T cell biology

Background:

• The thymus is crucial for T cell development, producing self-tolerant CD4+ and CD8+ T cells.
• Previous research has not compared transcriptomes of T cells within the thymus versus the periphery.

Purpose of the Study:

• To characterize and compare the transcriptomes of human T cells from the thymus and peripheral blood.
• To investigate age-related differences in peripheral T cell transcriptomes.
• To assess the expression of autoimmune disease-associated genes in thymic T cells.

Main Methods:

• High-throughput RNA sequencing was employed.
• Transcriptomes of primary single positive (SP) CD4+ and CD8+ T cells from infant thymus were analyzed.
• Transcriptomes of primary CD4+ and CD8+ T cells from infant and adult peripheral blood were analyzed.

Main Results:

• Thymic T cells displayed a higher number of uniquely expressed genes compared to peripheral T cells.
• More differentially expressed genes were found between thymic and blood T cells than between infant and adult blood T cells.
• Thymic T cells were enriched for cell cycle and replication genes; infant blood T cells for immune terms; adult blood T cells for inflammatory responses.

Conclusions:

• This study offers novel insights into human primary SP T cell transcriptomes within the thymus and their comparison to peripheral T cells.
• Most autoimmune disease-associated genes were expressed in T cell subsets, but approximately 11% were absent in adult peripheral blood T cells.