The human immune system is a complex network of cells categorized into two main branches: the innate immune system, which provides immediate defense, and the adaptive immune system, which mounts targeted, lasting responses. Among these are lymphocytes, a type of white blood cell. Natural Killer (NK) cells are a distinct lymphocyte belonging to the innate system, acting as first responders against cellular threats. The immune system contains numerous cell subsets, each distinguished by unique surface markers and functions.
Defining CD8 NK Cells
To understand specific immune cell types, scientists use a system called “Cluster of Differentiation,” or CD. These are proteins on a cell’s surface that function like identification tags for precise classification. Canonical NK cells are identified by being negative for the CD3 marker (CD3-) but positive for the CD56 marker (CD56+). A particular subset of these cells also expresses the CD8 protein, giving rise to the name CD8+ NK cells and setting them apart.
The shared CD8 marker can cause confusion with CD8+ T cells, also known as cytotoxic T lymphocytes. Although both express the CD8 protein, they belong to different immune branches. CD8+ T cells are part of the adaptive system and are defined by the CD3 marker. In contrast, CD8+ NK cells are part of the innate system and are CD3-negative, a fundamental difference that distinguishes them as separate cell lineages.
The expression of the CD8 marker on NK cells signifies a distinct cellular identity. Research indicates that about 30% of peripheral NK cells express the CD8α homodimer, a specific form of the protein. This expression is associated with enhanced survival capabilities, particularly when the cells are engaged in killing targets. Their existence highlights the specialization within the immune system, where cells can share markers while performing different roles.
Primary Functions and Mechanisms
The primary role of CD8+ NK cells is to identify and eliminate compromised host cells, such as those infected with viruses or that have become cancerous. They accomplish this through cytotoxicity, a direct-attack mechanism involving the release of proteins from granules. Two of these proteins are perforin and granzymes. Perforin punches pores into the target cell’s membrane, creating a channel for granzymes to enter.
Once inside, granzymes initiate programmed cell death, a process called apoptosis. This controlled demolition prevents the release of harmful substances from the dying cell that could damage surrounding healthy tissues. The perforin-granzyme system is a direct way for CD8+ NK cells to neutralize threats without prior sensitization. The presence of high levels of these cytotoxic molecules is a defining characteristic of this cell population.
Beyond direct cell killing, CD8+ NK cells perform a signaling function by secreting molecules called cytokines. One of the most important is Interferon-gamma (IFN-γ), which acts as an alert signal to orchestrate a broader immune response. The release of IFN-γ activates and recruits other immune cells, like macrophages and T cells, to the site of an infection or tumor. This function amplifies the body’s defenses, bridging the innate and adaptive immune reactions.
Role in Disease Response
CD8+ NK cells are effective in controlling certain diseases, particularly chronic viral infections where their numbers often expand. For instance, in individuals with long-term infections like Cytomegalovirus (CMV), the population of these cells increases significantly. This expansion is part of a sustained effort to control persistent viruses. Their ability to destroy host cells that have been turned into viral factories is important for limiting the spread of infection.
In cancer, CD8+ NK cells contribute to cancer immunosurveillance, where the immune system patrols the body and eliminates malignant cells. Research shows that a higher presence of these cytotoxic cells within some tumors correlates with better patient prognoses, suggesting their activity helps to suppress tumor growth. This natural anti-tumor function has made them a subject of interest for the development of cancer immunotherapies, which aim to boost the body’s own immune response.
Location and Memory-Like Properties
While CD8+ NK cells circulate in the bloodstream, they are found in higher concentrations in specific tissues like the liver. Their presence in such organs suggests they have specialized roles adapted to the local environment. For example, they contribute to immune surveillance in organs frequently exposed to foreign substances and pathogens from the digestive system.
A feature of some NK cell subsets, including many CD8+ NK cells, is their capacity for “memory-like” responses. Traditionally, immunological memory was considered exclusive to the adaptive immune system’s T and B cells. However, evidence shows that certain NK cells can persist long after an initial encounter and respond more robustly to a subsequent challenge. This trait blurs the conventional lines between innate and adaptive immunity.
This memory-like behavior is distinct from the classical memory of T and B cells but represents a significant advance in understanding innate immunity. The ability of CD8+ NK cells to form a long-lasting state of readiness suggests they can provide more effective and rapid protection against previously encountered pathogens. This discovery has opened new avenues for research, with scientists exploring how to harness these cells for therapeutic purposes like novel vaccines and immunotherapies.