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Susceptibility of peripheral blood mononuclear cells to apoptosis is correlated to plasma HIV load
M Karmochkine1, C Parizot, V Calvez
1Service de Médecine Interne, Hôpital de la Pitié-Salpêtrière, Paris, France.
Objectives:
To quantify spontaneous and activation-induced apoptosis in peripheral blood mononuclear cells (PBMC) of HIV-infected patients and to look for correlations between PBMC apoptosis levels, stages of HIV disease, CD4 count, and plasma viral load.
Study Populations:
75 consecutive inpatients and outpatients infected with HIV (mean CD4 count, 202 +/- 182 x 10(6)/L; mean plasma viral load, 4 +/- 1.29 log10 RNA copies/ml) and a control group composed of 18 healthy, HIV-negative adults.
Methods:
Spontaneous apoptosis was detected at the single-cell level by direct incorporation of fluorescein-deoxyuridine triphosphate (dUTP) in PBMC DNA strand breaks. Activation-induced apoptosis was determined after in vitro stimulation with anti-CD3 antibodies and interleukin-2 (IL-2).
Results:
Spontaneous apoptosis was low in patients and controls, whereas activation-induced apoptosis was significantly higher in HIV-infected patients (5.22 +/- 4.32% versus 2.46 +/- 1.77%, respectively; p = .009). The degree of activation-induced apoptosis was positively correlated with the plasma viral load (r = 0.29; p = .029) and negatively correlated with the CD4 count (r = -0.37; p = .0009). Although activation-induced apoptosis was significantly higher in patients fulfilling AIDS criteria, it did not differ significantly between patients with an acute AIDS-defining event and those with stable disease.
Conclusion:
Susceptibility of PBMC to apoptosis in HIV-1-infected patients is correlated to the plasma viral load and the stage of the disease.
Insights
Activation-induced apoptosis is elevated in HIV patients and correlates with viral load and disease stage. This finding highlights the impact of HIV on immune cell death and disease progression.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human Immunodeficiency Virus (HIV) infection is characterized by immune system dysfunction.
- Apoptosis, or programmed cell death, plays a critical role in immune homeostasis and pathogenesis.
- Peripheral blood mononuclear cells (PBMC) are key immune cells affected by HIV.
Purpose of the Study:
- To quantify spontaneous and activation-induced apoptosis in PBMCs of HIV-infected individuals.
- To investigate correlations between PBMC apoptosis levels, HIV disease stage, CD4+ T cell count, and plasma viral load.
Main Methods:
- PBMCs from 75 HIV-infected patients and 18 healthy controls were analyzed.
- Spontaneous apoptosis was measured by direct incorporation of fluorescein-deoxyuridine triphosphate (dUTP) into DNA strand breaks.
- Activation-induced apoptosis was assessed after in vitro stimulation with anti-CD3 antibodies and IL-2.
Main Results:
- Activation-induced apoptosis was significantly higher in HIV-infected patients compared to controls (5.22% vs. 2.46%, p = .009).
- Higher activation-induced apoptosis positively correlated with plasma viral load (r = 0.29, p = .029) and negatively with CD4+ T cell count (r = -0.37, p = .0009).
- Patients meeting AIDS criteria exhibited significantly higher activation-induced apoptosis.
Conclusions:
- PBMC susceptibility to apoptosis in HIV-1 infection is linked to plasma viral load and disease stage.
- These findings suggest that apoptosis dysregulation is a significant factor in HIV pathogenesis.