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In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 16, 2013
Costimulatory pathways mediate monocyte-dependent lymphocyte apoptosis in HIV
D E Lewis1, D S Ng Tang, X Wang
1Department of Microbiology and Immunology, Texas Children's Hospital, Houston, Texas 77030, USA. dlewis@bcm.tmc.edu
Clinical Immunology (Orlando, Fla.)
|March 17, 1999
Summary
HIV infection causes T cell apoptosis via antigen-presenting cells, not viremia. Abnormal antigen-presenting cells may drive T cell exhaustion, even with undetectable viral loads, impacting immune function in HIV patients.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- HIV infection leads to immune dysregulation and T cell apoptosis.
- Understanding the mechanisms of T cell death is crucial for managing HIV/AIDS.
Purpose of the Study:
- To investigate the mechanisms of T cell apoptosis in HIV-positive individuals.
- To identify the role of antigen-presenting cells and costimulatory signals in HIV-associated T cell death.
Main Methods:
- Annexin V binding assay to detect apoptosis in CD4(+) and CD8(+) T cells, and B cells.
- Analysis of FasL expression on monocytes.
- Monocyte depletion and blocking antibodies (anti-CD80, anti-CD86) to assess the role of antigen-presenting cells.
Main Results:
- CD4(+) and CD8(+) T cells showed early apoptosis in HIV+ individuals; B cell apoptosis occurred after incubation.
- CD8(+) T cell apoptosis correlated with lower CD4(+) T cell counts but not viremia levels.
- Antigen-presenting cells, specifically monocytes via CD80/CD86 costimulation, induced CD8(+) T cell apoptosis, while T cells mediated B cell apoptosis.
Conclusions:
- Antigen-presenting cell dysfunction contributes to CD8(+) T cell apoptosis and exhaustion in HIV infection.
- A distinct CD8(bright)CD28(dim) T cell population undergoes monocyte-induced apoptosis, potentially linked to immune exhaustion in patients with undetectable viremia.
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