Immune cells, the body’s defenders, constantly patrol to identify and neutralize threats like bacteria, viruses, and abnormal cells. These cells possess unique identifiers on their surfaces, much like different players on a sports team wear specific jerseys. These surface molecules are known as immune cell markers, and they allow scientists and medical professionals to distinguish between the many types of immune cells. These markers are proteins expressed either on the cell surface or sometimes within the cells themselves.
The Cluster of Differentiation Naming System
The scientific community established a standardized system to manage immune cell markers, known as the Cluster of Differentiation (CD) nomenclature. This system was introduced in Paris in 1982 at the 1st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA). Its purpose was to provide a universal language for classifying monoclonal antibodies developed against leukocyte surface molecules, preventing confusion across different laboratories worldwide.
Under this system, a specific CD number is assigned to a group of antibodies that recognize the same unique protein molecule found on a cell’s surface. For instance, “CD4” refers to a specific protein molecule, and “CD4 antibody” refers to the antibody that binds to it. Over 370 distinct CD clusters and subclusters have been identified, expanding beyond just white blood cells to include other cell types.
Key Markers of Major Immune Cells
Specific CD markers help distinguish between different families of immune cells, identifying their lineage.
T Cells
T cells, central to adaptive immunity, are identified by the presence of CD3 on their surface. This marker serves as a pan-T cell identifier. Within the T cell population, two major subsets are recognized by additional markers. Helper T cells, which coordinate immune responses, express CD4 alongside CD3. Conversely, cytotoxic T cells, responsible for directly eliminating infected or abnormal cells, express CD8 in combination with CD3.
B Cells
B cells, which mediate humoral immunity by producing antibodies, are identified by markers CD19 and CD20. CD19 is expressed earlier in B cell development and persists on plasmablasts and some antibody-secreting plasma cells, even after CD20 expression might be lost. CD20 is widely expressed on B cells during most stages of their development, from early pre-B cells up to their final differentiation, and plays a role in B cell activation and proliferation.
Natural Killer Cells
Natural Killer (NK) cells are innate immune cells that detect and kill virus-infected and tumor cells directly. They are identified by the co-expression of CD16 and CD56, along with the absence of CD3, which differentiates them from T cells. NK cells are further subdivided into two main populations based on the relative expression levels of these markers: CD56bright CD16dim/− cells, which are more cytokine-producing, and CD56dim CD16+ cells, known for their potent cytotoxic activity.
Monocytes/Macrophages
Monocytes are a type of white blood cell that circulates in the blood and can differentiate into macrophages in tissues. Both monocytes and macrophages are identified by the expression of CD14.
How Markers Reveal Cell Function and Status
Immune cell markers offer more than just a way to identify different cell types; they also provide insights into a cell’s current activity and functional state. Some markers, known as activation markers, appear on the cell surface or increase in quantity when an immune cell is actively responding to a stimulus, such as an infection or inflammation. These are distinct from the lineage markers that define a cell’s type.
For instance, CD69 is an early activation marker for lymphocytes, often appearing within hours of T cell receptor signaling. Another activation marker is CD25, part of the interleukin-2 (IL-2) receptor. CD25 is highly expressed on activated lymphocytes and regulatory T cells, signifying a later stage of activation and often indicating cell proliferation and responsiveness to IL-2. By observing these activation markers, scientists can gain a dynamic understanding of immune responses, determining whether cells are in a resting, fighting, or recovering state.
Practical Applications in Medicine
The ability to identify and analyze immune cell markers has transformed medical diagnostics and therapeutics. In diagnostics, a common application is monitoring the progression of Human Immunodeficiency Virus (HIV) infection. Flow cytometry, a laboratory technique, counts the absolute number of CD4 T cells in a patient’s blood, which ranges from 500 to 1400 cells/microliter in healthy individuals. A decrease in CD4 cell counts, particularly below 200 cells/microliter, indicates a weakened immune system and helps determine the need for prophylactic treatments against opportunistic infections, a criterion for an AIDS diagnosis.
Immune cell markers are also instrumental in diagnosing and classifying blood cancers like leukemias and lymphomas. These cancers involve the abnormal proliferation of white blood cells, and their specific marker profiles help distinguish between different subtypes. For example, chronic lymphocytic leukemia (CLL) cells often show expression patterns of CD5 and CD23 alongside pan-B cell markers like CD20, differing from normal B cells or other lymphomas. This detailed immunophenotyping helps oncologists tailor treatment strategies more effectively.
In therapeutics, immune cell markers serve as targets for advanced treatments. Chimeric Antigen Receptor (CAR) T cell therapy, for instance, re-engineers a patient’s own T cells to recognize and attack cancer cells. In B-cell leukemias and lymphomas, CD19 is a frequently targeted marker on cancerous B cells. CAR-T cells modified to express a receptor against CD19 have shown high remission rates in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Similarly, monoclonal antibodies are designed to bind specifically to certain immune cell markers, either to directly kill cancer cells or to modulate immune responses, as seen with rituximab targeting CD20 on B-cell lymphomas.