Related Experiment Video
Updated: Jun 14, 2026
10:23
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
Casp8p41 expression in primary T cells induces a proinflammatory response.
Julie A Taylor1, Nathan W Cummins, Gary D Bren
1Division of Infectious Diseases, Rochester, Minnesota, USA.
AIDS (London, England)
|March 20, 2010
Summary
HIV infection generates Casp8p41, a peptide that promotes cell death and enhances viral replication. This peptide also alters cytokine profiles, creating a pro-inflammatory environment characteristic of untreated HIV infection.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- HIV infection targets CD4 T cells.
- HIV protease cleaves procaspase 8 to produce Casp8p41.
- Casp8p41 induces apoptosis and activates NFkappaB, enhancing HIV replication.
Purpose of the Study:
- To investigate the impact of Casp8p41-induced NFkappaB activation on the cytokine profile of cells expressing Casp8p41.
- To determine if Casp8p41 influences host gene transcription and cytokine production in HIV-infected cells.
Main Methods:
- Microarray analysis to identify upregulated genes.
- Cytokine quantification using ELISAs or similar assays.
- Western blot and flow cytometry for protein validation and cellular analysis.
Main Results:
- Microarray analysis revealed 259 upregulated genes upon Casp8p41 expression.
- Casp8p41 expression increased Interleukin (IL)-2, IL-15, Tumor Necrosis Factor (TNF), and IL-1RA.
- Reduced levels of granulocyte macrophage colony-stimulating factor and Interferon (IFN)-gamma were observed.
- Flow cytometry confirmed Casp8p41 co-association with elevated TNF in HIV-infected cells.
Conclusions:
- Casp8p41 expression in HIV-infected CD4 T cells promotes apoptosis and enhances viral replication.
- Casp8p41 induces a pro-inflammatory cytokine milieu.
- This cytokine profile is characteristic of untreated HIV infection.
Related Concept Videos
01:24Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
01:22T Cell Activation and Clonal Selection
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
01:24T Cell Types and Functions
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:27Cytotoxic T Cells-mediated Immune Response
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...