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Preparation and Use of HIV-1 Infected Primary CD4+ T-Cells as Target Cells in Natural Killer Cell Cytotoxic Assays
Published on: March 14, 2011
Mechanisms of HIV-associated lymphocyte apoptosis
A D Badley1, A A Pilon, A Landay
1Ottawa Hospital Research Institute and the Division of Infectious Diseases, Ottawa Hospital, Ottawa, Ontario, Canada. abadley@ottawahospital.on.ca
Insights
Human immunodeficiency virus (HIV) infection causes T-cell death through apoptosis, impairing immune defenses. New therapies reduce this cell death but don't clear viral reservoirs, necessitating further research into HIV-induced apoptosis.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human immunodeficiency virus (HIV) infection leads to a decline in CD4 T-cells, compromising immune function.
- Apoptosis, or programmed cell death, is observed in both HIV-infected and uninfected T-cells during HIV disease.
- Multiple mechanisms contribute to HIV-associated lymphocyte apoptosis, including chronic immune activation and viral protein interactions.
Purpose of the Study:
- To investigate the mechanisms of T-cell apoptosis in HIV infection.
- To understand the role of apoptosis in the development of viral reservoirs.
- To explore the impact of current HIV therapies on apoptosis and viral reservoirs.
Main Methods:
- Analysis of T cells from HIV-infected patients and in vitro HIV-infected T cells.
- Examination of various mechanisms contributing to lymphocyte apoptosis.
- Evaluation of the effects of current HIV therapies on T-cell apoptosis and viral replication.
Main Results:
- A significant proportion of T cells undergo apoptosis in HIV infection.
- Mechanisms include gp120/160 ligation, cytotoxic ligand production, and direct viral infection.
- HIV infection of resting cells may contribute to viral reservoir formation.
- Current therapies reduce T-cell apoptosis and viral replication but do not eliminate viral reservoirs.
Conclusions:
- HIV infection profoundly impacts T-cell homeostasis through apoptosis.
- Understanding the regulation of apoptosis is crucial for developing effective HIV treatments.
- Novel immune-based therapies targeting HIV-induced apoptosis are needed to improve patient outcomes and address viral reservoirs.
Abstract:
Infection with the human immunodeficiency virus (HIV) is associated with a progressive decrease in CD4 T-cell number and a consequent impairment in host immune defenses. Analysis of T cells from patients infected with HIV, or of T cells infected in vitro with HIV, demonstrates a significant fraction of both infected and uninfected cells dying by apoptosis. The many mechanisms that contribute to HIV-associated lymphocyte apoptosis include chronic immunologic activation; gp120/160 ligation of the CD4 receptor; enhanced production of cytotoxic ligands or viral proteins by monocytes, macrophages, B cells, and CD8 T cells from HIV-infected patients that kill uninfected CD4 T cells; and direct infection of target cells by HIV, resulting in apoptosis. Although HIV infection results in T-cell apoptosis, under some circumstances HIV infection of resting T cells or macrophages does not result in apoptosis; this may be a critical step in the development of viral reservoirs. Recent therapies for HIV effectively reduce lymphoid and peripheral T-cell apoptosis, reduce viral replication, and enhance cellular immune competence; however, they do not alter viral reservoirs. Further understanding the regulation of apoptosis in HIV disease is required to develop novel immune-based therapies aimed at modifying HIV-induced apoptosis to the benefit of patients infected with HIV.
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