The protein marker CD56, or Cluster of Differentiation 56, is found on the surface of various cells. Scientifically named Neural Cell Adhesion Molecule 1 (NCAM1), this protein plays a role in how cells interact and adhere to one another. While its functions extend to the nervous system, its presence on immune cells is of particular interest in immunology. The CD56 marker allows scientists and clinicians to identify and isolate specific cell populations, providing insights into the immune system.
Understanding CD56 Positive Cells
The CD56 marker is most prominently expressed on Natural Killer (NK) cells, a component of the innate immune system. While NK cells are the primary population identified by this marker, other cells can also be CD56-positive (CD56+), including a subset of T cells and certain cells within the nervous system. This expression across different cell types highlights the protein’s original name related to neural cell adhesion. In immunology, the study of CD56 focuses on its role in defining NK cells.
Human NK cells are divided into two main subtypes based on the intensity of CD56 expression on their surface: CD56dim and CD56bright cells. The CD56dim population is the most abundant, making up about 90% of the NK cells found circulating in the peripheral blood. These cells are considered mature and are primarily equipped for cytotoxic, or cell-killing, functions.
In contrast, CD56bright NK cells are less common in the bloodstream and are found in secondary lymphoid organs like lymph nodes and tonsils. This population is considered less mature and serves a significant immunoregulatory role. Instead of being potent killers, CD56bright cells are major producers of cytokines, which are signaling proteins that coordinate the immune response. The distinct locations and characteristics of these subsets suggest they perform different, yet complementary, roles in immune defense.
The Immune Roles of CD56 Cells
CD56-positive NK cells are rapid responders within the innate immune system, providing an immediate line of defense against cellular threats. Their function does not require prior sensitization, allowing them to act quickly against newly encountered dangers. This enables them to control infections and eliminate abnormal cells before the slower adaptive immune system has been fully activated.
A primary function of these cells is recognizing and destroying virally infected and tumor cells through cytotoxicity. One mechanism is “missing-self” recognition. Healthy cells display Major Histocompatibility Complex (MHC) class I molecules on their surface, which act as a “self” signal that NK cells recognize via inhibitory receptors, preventing an attack. When a cell is infected or becomes cancerous, it often reduces its MHC class I expression, and this absence of “self” is detected by NK cells, triggering their killing function.
Another cytotoxic mechanism is antibody-dependent cell-mediated cytotoxicity (ADCC). In this process, antibodies produced by the adaptive immune system coat a target cell. The CD16 receptor on CD56dim NK cells binds to these antibodies, activating the NK cell to release cytotoxic granules that induce the target cell’s death. This function links the innate power of NK cells with the specificity of the adaptive immune response.
Beyond direct killing, CD56+ cells shape the immune landscape by producing signaling molecules. CD56bright NK cells are adept at releasing cytokines, most notably interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). These cytokines can activate other immune cells, such as macrophages and T cells, enhancing their ability to clear pathogens. By orchestrating the actions of other cells, CD56+ cells help mount a coordinated defense.
CD56 Cells and Health Conditions
The functions of CD56+ NK cells give them a role in managing health conditions, including viral infections. They are among the first responders to viruses such as herpesviruses, influenza, and HIV. In HIV infection, NK cells can limit viral spread by killing infected cells and secreting chemokines that block the virus from entering target cells. The number and function of these cells can become dysregulated during chronic infections, impacting long-term control.
These cells are involved in cancer immune surveillance, a process where the immune system finds and eliminates malignant cells before they form tumors. Their ability to kill cells that have lost MHC class I expression is a defense against tumors attempting to evade the immune system. The presence and activity level of NK cells within a tumor can indicate how effectively the body is fighting the cancer.
The role of CD56+ cells extends to autoimmune diseases and pregnancy. In autoimmunity, where the immune system mistakenly attacks the body’s own tissues, NK cells can have a dual role. Depending on the disease, they might contribute to tissue damage through their cytotoxic functions or help regulate and suppress other overactive immune cells.
During pregnancy, a specialized population of CD56bright NK cells, known as uterine NK (uNK) cells, accumulates in the uterine lining. These cells are not cytotoxic but instead play a part in the successful development of the placenta. They help remodel maternal arteries to ensure an adequate blood supply to the growing fetus, a function necessary for a healthy pregnancy.
Clinical Significance of CD56 Cells
In clinical settings, the CD56 marker is a valuable tool for diagnostics and monitoring. Flow cytometry is used to count the number of CD56+ cells, particularly NK cells, in a patient’s blood sample. This count helps assess a person’s immune status, which can be relevant in immunodeficiency disorders or for monitoring therapies.
The CD56 marker is also used in the diagnosis and classification of certain cancers. It is a defining feature of hematological malignancies that arise from NK cells, such as aggressive NK-cell leukemia or certain types of lymphoma. CD56 can also be expressed on other cancer cells where it is not normally found, serving as a diagnostic clue or prognostic indicator.
The number and activity of CD56+ cells can have prognostic value, helping to predict the course of a disease. For example, in multiple myeloma, the absence of CD56 expression on malignant plasma cells is associated with a poorer prognosis. Conversely, the presence of tumor-infiltrating lymphocytes that express CD56 has been linked to better clinical outcomes in some breast cancers.
There is growing interest in harnessing CD56+ NK cells for therapeutic purposes, especially in oncology. One approach is adoptive cell therapy, where NK cells are isolated, expanded in a lab, and then infused back into a patient to fight cancer. A more advanced strategy involves genetically engineering NK cells to express chimeric antigen receptors (CARs). These CAR-NK cells are designed to recognize specific proteins on tumor cells, combining the killing power of NK cells with targeted precision.