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Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.
Published on: September 1, 2015
Study of CD4+CD8+ double positive T-lymphocyte phenotype and function in Indian patients infected with HIV-1
Neeraj K Chauhan1, Madhu Vajpayee, Kamalika Mojumdar
1Department of Microbiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Insights
Chronic HIV-1 infection increases double positive T cells, which show higher activation and exhaustion. This finding is crucial for understanding HIV immunopathology and disease progression.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- CD4+CD8+ double positive T cells are a minor lymphocyte population.
- HIV-1 infection causes generalized immune activation, necessitating study of double positive T cells in HIV immunopathology.
Purpose of the Study:
- To compare the frequency of double positive T cells in HIV-infected individuals versus controls.
- To assess activation and exhaustion markers (CD38, HLA-DR, PD-1) on double positive T cells in HIV.
- To investigate the phenotype and cytokine secretion of HIV-1 specific double positive T cells.
Main Methods:
- Flow cytometry was used to quantify double positive T cells and analyze marker expression.
- Comparison of cell populations between HIV-infected patients with different CD4+ T cell counts and healthy controls.
- Assessment of HIV-1 specific T cell responses.
Main Results:
- A higher frequency of double positive T cells was observed in advanced HIV disease (CD4+ < 200 cells/µl).
- Double positive T cells from symptomatic HIV patients exhibited increased activation and exhaustion markers (CD38, PD-1).
- Expression of CD38 and PD-1 on double positive T cells correlated with HIV viremia and inversely with CD4+ T cell counts.
Conclusions:
- HIV infection significantly expands the double positive T cell population.
- These expanded double positive T cells display heightened activation and exhaustion phenotypes.
- The findings highlight the role of double positive T cells in HIV pathogenesis and immune dysfunction.
Abstract:
CD4+CD8+ double positive T cells represent a minor peripheral blood lymphocyte population. CD4+ expression on CD8+ T cells is induced following cellular activation, and as chronic HIV-1 infection is associated with generalized immune activation, double positive T cells studies have become necessary to understand the immunopathology of human immunodeficiency virus (HIV). The frequency of double positive T cells in persons infected with HIV was studied in comparison to uninfected controls. Further, the expression of CD38, HLA-DR, and programmed death (PD)-1 on these cells were ascertained. HIV-1 specific double positive T cells were also studied for their cytokine secretory ability and phenotype. A significantly higher double positive cell population was observed in the patients with advanced HIV disease (CD4+ T cell counts below 200 cells/µl), as compared to patients with CD4+ T cell counts above 500 cells/µl. Double positive T cells from patients with symptomatic HIV disease had a significantly increased activation and exhaustion levels, compared to asymptomatic subjects and to single positive T cells from the same subjects. HIV-1 specific double positive T cells showed further increase in CD38 and PD-1 expression levels. The proportion of CD38 and PD-1 expressing total and HIV-1 specific double positive T cells correlated positively with HIV-1 plasma viremia and negatively with CD4+ T cell counts. HIV infection results in a marked increase of double positive T cell population, and this cell population shows higher level of activation and exhaustion (increased PD-1 expression) compared to the single positive CD4+ and CD8+ T cells.

