Reduction in terminally differentiated T cells in virologically controlled HIV-infected aging patients on long-term antiretroviral therapy

PLoS One. 2018 Jun 13;13(6):e0199101. doi: 10.1371/journal.pone.0199101. eCollection 2018.

Abstract

Several studies have shown an increased accumulation of terminally differentiated T cells during HIV infection, suggestive of exhaustion/senescence, causing dysregulation of T cell homeostasis and function and rapid HIV disease progression. We have investigated whether long-term antiretroviral therapy (ART), which controls viremia and restores CD4 T cell counts, is correlated with reduction in terminally differentiated T cells, improved ratios of naïve to memory and function of T cells in 100 virologically controlled HIV-infected patients. We show that while the median frequencies of terminally differentiated CD4+ and CD8+ T cells (CD28-, CD27-, CD57+ and CD28-CD57+), were higher in the virologically controlled HIV-infected patients' cohort compared with uninfected individuals' cohort, the frequencies of these cells significantly decreased with increasing CD4 T cell counts in HIV-infected patients. Although, the naïve CD4+ and CD8+ T cells were lower in HIV patients' cohort than uninfected cohort, there was a significant increase in both naïve CD4+ and CD8+ T cells with increasing CD4 T cell counts in HIV-infected patients. The underlying mechanism behind this increased naïve CD4+ and CD8+ T cells in HIV-infected patients was due to an increase in recent thymic emigrants, CD4+CD31+, as compared to CD4+CD31-. The CD4+ T cells of HIV-infected patients produced cytokines, including IL-2, IL-10 and IFN-γ comparable to uninfected individuals. In conclusion, virologically controlled HIV-infected patients on long-term ART show a significant reduction in terminally differentiated T cells, suggestive of decreased exhaustion/senescence, and improvement in the ratios of naïve to memory and function of T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD57 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation
  • Cellular Senescence
  • Cytokines / metabolism
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • Humans
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Anti-HIV Agents
  • CD57 Antigens
  • Cytokines

Grants and funding

This work was supported by a grant (ADHS14-082984) from the Arizona Biomedical Research Commission, Arizona Department of Health Services. The authors received no specific funding for this work.