Impaired CD4+T cell differentiation in HIV-1 infected patients receiving early anti-retroviral therapy

Differentiation of CD4+ T naive (TN) into central memory (TCM) cells involves extensive molecular processes. We compared the transcriptomes of CD4+ TN and TCM cells from HIV-1 infected patients receiving early antiretroviral therapy (ART; EA; n = 13) and controls (n = 15). Comparison of protein coding genes between TCM and TN revealed 533 and 82 differentially expressed genes (DEGs) in controls and EA, respectively. A high degree of transcriptional complexity was detected during transition of CD4+ T-N to T-CM cells in controls involving 70 TFs, 20 master regulators of T cell differentiation (TBX21, GATA3, RARA, FOXP3, RORC); in EA only 7 TFs were modulated with expression of several master regulators remaining unchanged during differentiation. Analysis of interactions between modulated TFs and target genes revealed important regulatory interactions missing in EA group. We conclude that T cell differentiation in EA patients is impaired due to reduced modulation of genes involved in transition from CD4+ TN to TCM cells.

Automated summary

This study compared the transcriptomes of CD4+ T naive (TN) and central memory (TCM) cells between HIV-1 infected patients receiving early antiretroviral therapy (EA) and controls. The results showed that there is a high degree of transcriptional complexity during the transition from CD4+ T-N to T-CM cells in controls, while in EA patients, the modulation of transcription factors is reduced, resulting in impaired T cell differentiation.