Tracking global gene expression responses in T cell differentiation

Upon receiving antigens from the innate immune cells, CD4⁺ T cells differentiate into distinct effector cells. To probe the global responses of distinct effector cells, we analyzed transcriptome-wide expressions of Th₁, Th₂, T_reg and Th₁₇ using Pearson correlation, entropy and principal component analyses, with Th₀ as a control. Although the global response of Th₀ was quite distinct from Th₁₇, surprisingly, it was highly similar to Th₁, Th₂ and T_reg. Moreover, 8 major temporal groups consisting of 5704 differentially expressed genes were revealed for both Th₀ and Th₁₇. Gene functional enrichment analysis showed immune responses and metabolic processes were mainly activated between Th₀ and Th₁₇, while genes related to cell cycle and replication were differentially regulated. Moreover, we found the upregulation of several novel genes for Th₀ and Th₁₇. Overall, we deduce that Th₀ is globally similar to Th₁, Th₂ and T_reg. Our results indicate that Th₀ is a differentiated state and, therefore, may not be used as a control cell type.