In HIV-infected individuals, highly active antiretroviral therapy (HAART) reduces the viral load, which contributes to a CD4+ T-cell count increase and results in both higher life expectancy and better quality of life. Nevertheless, the extent of immune system regeneration varies between patients. In most subjects receiving HAART, there has been a moderate growth of the CD4+ T-cell pool size. However, 20 to 30% of people receiving treatment develop an immunological non-response. In immunological non-responders (INRs), the number of CD4+ T-lymphocytes remains significantly reduced and does not increase despite years of virologically successful treatment. One of the leading concerns regarding INRs is their increased risk of developing non-AIDS-related and AIDS-associated diseases due to their immunosuppressed status, thus leading to premature death.
The efficiency of CD4+ T-lymphocyte pool regeneration depends on the ratio of two processes: cell division and death. Lymphocytes increase in number through lymphopenia-induced homeostatic proliferation, which exceeds the rate of death in infected and by-stander activated T-cells. Notably, the frequency of cycling CD4+ T-lymphocytes is higher in INRs than in HIV-infected subjects with a standard response to treatment. However, in INRs, a significant proportion of CD4+ T-cells entering mitosis die before finishing the cell cycle. Evidently, the low proliferation productivity of these lymphocytes is one of the major reasons for the ineffective immune system regeneration during HAART.
A critical factor ensuring productive cell division is metabolic remodeling. The violation at any level of the metabolic regulation can lead to cell death and reduce the effectiveness of the immune system restoration in HIV-infected patients. The study of the metabolic features of T-lymphocytes entering the regeneration process is necessary for developing novel approaches to the successful treatment of HIV infection. This Research Topic also aims to increase our understanding of the underlying mechanisms leading to immunological non-response and design effective individualized treatment strategies.
The following article types are welcome for submission: Original Research, Brief Research Report, Reviews, Mini-Reviews, Systematic Reviews, Perspective, Opinion, and Hypothesis. We appreciate contributions that include, but are not limited to, the following topics:
• Metabolism of quiescent and proliferating T-lymphocytes
• Genetic and epigenetic features of T-cells in HIV-infected individuals with different efficiencies of immune regeneration during treatment
• Cell cycle control in T-lymphocytes
• Effects of viral and bacterial products on T-cell proliferation and metabolism
• Influence of pro-inflammatory factors on the mitotic activity and metabolism of T-cells
• Effects of antiretroviral drugs on T-cell metabolism and proliferation
• The link between immune reconstitution and the microbiome
• New approaches to immunodeficiency correction in immunological non-responders
In HIV-infected individuals, highly active antiretroviral therapy (HAART) reduces the viral load, which contributes to a CD4+ T-cell count increase and results in both higher life expectancy and better quality of life. Nevertheless, the extent of immune system regeneration varies between patients. In most subjects receiving HAART, there has been a moderate growth of the CD4+ T-cell pool size. However, 20 to 30% of people receiving treatment develop an immunological non-response. In immunological non-responders (INRs), the number of CD4+ T-lymphocytes remains significantly reduced and does not increase despite years of virologically successful treatment. One of the leading concerns regarding INRs is their increased risk of developing non-AIDS-related and AIDS-associated diseases due to their immunosuppressed status, thus leading to premature death.
The efficiency of CD4+ T-lymphocyte pool regeneration depends on the ratio of two processes: cell division and death. Lymphocytes increase in number through lymphopenia-induced homeostatic proliferation, which exceeds the rate of death in infected and by-stander activated T-cells. Notably, the frequency of cycling CD4+ T-lymphocytes is higher in INRs than in HIV-infected subjects with a standard response to treatment. However, in INRs, a significant proportion of CD4+ T-cells entering mitosis die before finishing the cell cycle. Evidently, the low proliferation productivity of these lymphocytes is one of the major reasons for the ineffective immune system regeneration during HAART.
A critical factor ensuring productive cell division is metabolic remodeling. The violation at any level of the metabolic regulation can lead to cell death and reduce the effectiveness of the immune system restoration in HIV-infected patients. The study of the metabolic features of T-lymphocytes entering the regeneration process is necessary for developing novel approaches to the successful treatment of HIV infection. This Research Topic also aims to increase our understanding of the underlying mechanisms leading to immunological non-response and design effective individualized treatment strategies.
The following article types are welcome for submission: Original Research, Brief Research Report, Reviews, Mini-Reviews, Systematic Reviews, Perspective, Opinion, and Hypothesis. We appreciate contributions that include, but are not limited to, the following topics:
• Metabolism of quiescent and proliferating T-lymphocytes
• Genetic and epigenetic features of T-cells in HIV-infected individuals with different efficiencies of immune regeneration during treatment
• Cell cycle control in T-lymphocytes
• Effects of viral and bacterial products on T-cell proliferation and metabolism
• Influence of pro-inflammatory factors on the mitotic activity and metabolism of T-cells
• Effects of antiretroviral drugs on T-cell metabolism and proliferation
• The link between immune reconstitution and the microbiome
• New approaches to immunodeficiency correction in immunological non-responders
