CD8+ T cells are specialized white blood cells, or lymphocytes, that function as the primary cellular defense mechanism within the adaptive immune system. These cells patrol the body, directly confronting threats that hide inside other cells, such as viral infections or cancerous transformation. They are often called cytotoxic T lymphocytes (CTLs) because they induce death in target cells. The CD8+ T cell’s purpose is to identify and eliminate compromised host cells, preventing the spread of disease or tumor growth.
Identity and Target Recognition
The CD8+ T cell is named for the CD8 co-receptor protein displayed on its surface. This co-receptor acts as a molecular anchor, helping the T cell receptor (TCR) bind securely to its target. The CD8 molecule recognizes a conserved portion of the Major Histocompatibility Complex (MHC) Class I molecule.
Target identification relies on MHC Class I molecules, which are present on nearly all nucleated cells in the body. These molecules constantly sample small peptide fragments from proteins synthesized inside the cell. If the cell is healthy, MHC I displays “self” peptides derived from normal proteins, which the CD8+ T cell ignores.
If a cell is infected or cancerous, it produces foreign or abnormal proteins. Fragments of these foreign proteins are loaded onto MHC Class I molecules and displayed on the cell surface, flagging the cell as compromised. The CD8+ T cell’s TCR scans these MHC I-peptide complexes. When a foreign peptide is detected, the CD8 co-receptor stabilizes the connection, initiating a specific immune response that targets only cells harboring an internal threat.
The Cytotoxic Killing Mechanism
Once the CD8+ T cell locks onto a target cell displaying a foreign antigen, it initiates cytotoxicity. The T cell forms a tight junction with the target, called an immunological synapse, to ensure the precise delivery of toxic molecules. Within this synapse, the T cell polarizes its internal structures to aim specialized storage compartments, called lytic granules, directly at the target cell membrane.
These lytic granules are released via granule exocytosis. The primary component released is perforin, a pore-forming protein. Perforin molecules insert themselves into the target cell’s membrane and polymerize, creating channels that breach the cell’s integrity.
These perforin channels allow entry for digestive enzymes, primarily granzyme B, also contained in the granules. Granzyme B activates a cascade of enzymes, such as caspases, which trigger controlled cell death, or apoptosis. This process dismantles the infected or cancerous cell, neutralizing the threat without causing significant inflammation. The CD8+ T cell then detaches and moves on to eliminate another target.
Essential Roles in Viral and Cancer Immunity
CD8+ T cells are indispensable for controlling acute viral infections, such as influenza. They act as the primary defense against pathogens that replicate inside host cells, where antibodies cannot reach. By quickly destroying virally infected cells, these cytotoxic T cells limit the spread of the virus, leading to the resolution of the illness.
CD8+ T cells also perform continuous immune surveillance against cancer. They patrol tissues, checking for abnormal or mutated proteins displayed by cancer cells on their MHC Class I molecules. This surveillance mechanism detects and eliminates newly emerging tumor cells before they can establish a macroscopic tumor, acting as a natural form of cancer prevention.
The adaptive immune response relies on the formation of long-lived memory CD8+ T cells after an initial encounter with a threat. A subset of activated CD8+ T cells differentiates into memory cells that persist in the body for years. These memory cells are strategically distributed, including tissue-resident memory cells in peripheral tissues like the lungs or skin.
Upon re-exposure to the same threat, memory cells activate far more rapidly than their naive counterparts. This accelerated response allows the immune system to mount a powerful defense almost instantly, often clearing the infection or eliminating the tumor before symptoms appear. Many modern vaccines aim to induce this durable CD8+ T cell memory response.
Therapeutic Applications
The potent killing capacity of CD8+ T cells has been harnessed to create transformative new therapies, particularly in oncology.
CAR T-Cell Therapy
One significant advance is Chimeric Antigen Receptor (CAR) T-cell therapy, which genetically engineers a patient’s own T cells. T cells are extracted and modified in a laboratory to express a synthetic receptor, the CAR, on their surface. This custom-built CAR allows the T cell to recognize specific antigens found on cancer cells, such as CD19, independent of the natural MHC presentation system. The engineered CAR T cells are multiplied and infused back into the patient, creating a highly targeted, living drug that actively seeks out and destroys tumor cells. This therapy has demonstrated success in treating several types of hematological malignancies, including leukemias and lymphomas.
Vaccine Development
CD8+ T cells are also central to modern vaccine designs targeting chronic infections and cancer. While traditional vaccines focus on generating protective antibodies, newer generations aim to elicit a strong and long-lasting CD8+ T cell response. By presenting specific fragments of viral or tumor proteins, these vaccines prime the CD8+ T cells to recognize and attack infected or cancerous cells immediately upon future exposure. This focus on cellular immunity provides more effective and durable protection against complex diseases.