Related Experiment Video
Updated: Oct 7, 2025
08:50
Scalable Biomanufacturing Workflow to Produce and Isolate Natural Killer Cell-Derived Extracellular Vesicle-Based Cancer Biotherapeutics
Published on: August 16, 2024
922
Intra- and Extracellular Effector Vesicles From Human T And NK Cells: Same-Same, but Different?
Marcus Lettau1,2, Ottmar Janssen1
1Molecular Immunology, Institute of Immunology, University Hospital Schleswig-Holstein, Kiel, Germany.
Frontiers in Immunology
|January 10, 2022
Summary
Cytotoxic T lymphocytes and Natural Killer cells release effector proteins via distinct vesicles. Extracellular vesicles (EVs) share protein profiles with intracellular vesicles, suggesting a broader role in cell communication.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Cytotoxic T lymphocytes (CTL) and Natural Killer (NK) cells eliminate target cells using shared effector proteins.
- Initially, all cytotoxic proteins were thought to be stored in a single compartment, secretory lysosomes (LREV), and released at the immunological synapse.
Purpose of the Study:
- To investigate the heterogeneity of effector protein storage and release mechanisms in CTLs and NK cells.
- To explore the relationship between intracellular effector vesicles and extracellular vesicles (EVs) in immune cell communication.
Main Methods:
- Analysis of enriched lysosome-related effector vesicles (LREV) from CTLs and NK cells.
- Distinguishing LREV populations based on protein content and degranulation signaling requirements (PKC-dependent vs. Ca2+-dependent).
- Comparative proteomic analysis of intracellular LREV and extracellular vesicles (EVs) derived from CTLs and NK cells.
Main Results:
- LREV exhibit uneven effector distribution, with distinct populations identified: light vesicles (FasL, 15 kDa granulysin) released PKC-dependently, and dense granules (perforin, granzymes, 9 kDa granulysin) released Ca2+-dependently.
- Both LREV types store and transport diverse immunomodulatory proteins beyond cytolytic effectors.
- CTL- and NK cell-derived EVs share a significant protein overlap with intracellular vesicles, mirroring the cells of origin.
Conclusions:
- Cytotoxic effector release is mediated by distinct LREV populations with differential signaling requirements.
- Intracellular and extracellular vesicles are closely related, with EVs potentially serving as systemic communicators.
- EVs may act as additional effector vesicles or intercellular communicators beyond the immunological synapse.
Related Concept Videos
01:25Immune Surveillance by NK Cells and Phagocytes
4.8K
Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
4.8K
01:28Cells of the Innate Immune Response
5.4K
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...
5.4K
01:29Immune Response Against Viral Pathogens
1.0K
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
1.0K
01:27Cytotoxic T Cells-mediated Immune Response
3.8K
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...
3.8K
01:24T Cell Types and Functions
1.5K
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...
1.5K
01:38Intralumenal Vesicles and Multivesicular Bodies
3.9K
Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.9K