Altered differentiation is central to HIV-specific CD4+ T cell dysfunction in progressive disease.
Antigoni MorouElsa Brunet-RatnasinghamMathieu DubéRoxanne CharleboisEloi MercierSam DarkoNathalie BrassardKrystelle Nganou-MakamdopSahaana ArumugamGabrielle Gendron-LepageLifei YangJulia NiesslAmy E BaxterJames M BillingsleyPremeela A RajakumarFrançois LefebvreR Paul JohnsonCécile TremblayJean-Pierre RoutyRichard T WyattAndrés FinziDaniel C DouekDaniel E KaufmannPublished in: Nature immunology (2019)
Dysfunction of virus-specific CD4+ T cells in chronic human infections is poorly understood. We performed genome-wide transcriptional analyses and functional assays of CD4+ T cells specific for human immunodeficiency virus (HIV) from HIV-infected people before and after initiation of antiretroviral therapy (ART). A follicular helper T cell (TFH cell)-like profile characterized HIV-specific CD4+ T cells in viremic infection. HIV-specific CD4+ T cells from people spontaneously controlling the virus (elite controllers) robustly expressed genes associated with the TH1, TH17 and TH22 subsets of helper T cells. Viral suppression by ART resulted in a distinct transcriptional landscape, with a reduction in the expression of genes associated with TFH cells, but persistently low expression of genes associated with TH1, TH17 and TH22 cells compared to the elite controller profile. Thus, altered differentiation is central to the impairment of HIV-specific CD4+ T cells and involves both gain of function and loss of function.
Keyphrases
- antiretroviral therapy
- hiv infected
- human immunodeficiency virus
- hiv positive
- hiv infected patients
- hiv aids
- hepatitis c virus
- induced apoptosis
- poor prognosis
- oxidative stress
- dna methylation
- body composition
- gene expression
- hiv testing
- cell proliferation
- south africa
- high throughput
- multiple sclerosis
- endoplasmic reticulum stress
- regulatory t cells
- signaling pathway