Related Experiment Video
Updated: Jun 19, 2026
09:18
Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Activation-induced CD154 expression abrogates tolerance induced by apoptotic cells.
Prajwal Gurung1, Tamara A Kucaba, Thomas A Ferguson
1Department of Urology, University of Iowa, Iowa City, IA 52242-1089, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 21, 2009
Summary
The state of T cells (naive or activated) encountering antigens alongside apoptotic cells determines immune tolerance or response. CD154 (CD40 ligand) and IL-12 are key factors influencing this immune outcome.
Area of Science:
- Immunology
- Cellular Biology
- Immune Response
Background:
- The immune system's response to antigens (Ag) depends on the context of T cell activation.
- Apoptotic cells can influence immune responses, leading to either tolerance or immunity.
Purpose of the Study:
- To investigate how the activation state of apoptotic cells impacts immune outcomes.
- To elucidate the roles of CD154 and IL-12 in determining immune responses to antigens presented by apoptotic cells.
Main Methods:
- In vivo studies using naive and activated apoptotic T cells injected intravenously.
- Experiments involving CD154 knockout (KO) T cells and anti-CD40 monoclonal antibody (mAb).
- In vitro co-culture of dendritic cells with activated apoptotic T cells and studies using IL-12p40 KO mice or IL-12 neutralization.
Main Results:
- Naive apoptotic cells induced tolerance, while activated apoptotic cells induced immunity.
- CD154 deficiency in apoptotic T cells abrogated immunity, and anti-CD40 mAb restored it.
- CD154-dependent IL-12 production by dendritic cells was crucial for activated apoptotic T cells to induce immunity.
Conclusions:
- CD154 expression on apoptotic T cells is a critical determinant of immune response outcomes.
- The interplay between CD154, IL-12, and the activation state of apoptotic cells dictates tolerance versus immunity.
- The balance of naive versus activated apoptotic cells influences the induction of productive immune responses.
More Related Videos
Related Concept Videos
01:17Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
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...
01:27Cytotoxic 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...
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...
01:30Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
01:28Cells of the Innate Immune Response
The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...