The immune system serves as the body’s defense network. Among its many specialized cells, T cells play a central role, identifying and neutralizing infected or abnormal cells. A molecule known as CD44 is often found on the surface of T cells, acting as a marker and influencing their behavior in various immune processes.
Understanding CD44 and Its Presence on T Cells
CD44 is a cell surface glycoprotein, a protein with attached sugar chains on the outer membrane of cells. It functions as an adhesion molecule, helping cells bind to their surroundings or to other cells. This molecule is widely expressed across many cell types, including leukocytes, endothelial cells, fibroblasts, and keratinocytes.
A primary molecule that CD44 interacts with is hyaluronic acid (HA), a component of the extracellular matrix. This interaction is important for cell movement and signaling within tissues. The specific form of CD44, known as CD44 standard, is the most common and is expressed on T cells. The levels of CD44 on T cell surfaces can change depending on their state of activation. This dynamic expression indicates T cell activity and helps guide their movement and functions.
CD44 T Cells in Immune Activation and Memory
CD44 expression levels on T cells change when these cells transition from a resting, “naive” state to an activated or “effector” state. Upon encountering an antigen, naive T cells increase their CD44 expression, becoming CD44-high. This upregulation is a sign of T cell activation and is maintained as these cells differentiate into effector and memory T cells.
The interaction of CD44 with hyaluronic acid (HA) is important for T cell migration. CD44 helps T cells “roll” along the inner lining of blood vessels and then adhere, allowing them to exit the bloodstream and move into inflamed or infected tissues. This process, called extravasation, is important for directing immune cells to sites of infection or inflammation. CD44 can also enhance T cell receptor signaling, important for T cell activation and the production of specific immune molecules.
CD44 also serves as a marker for memory T cells, which are long-lived cells that provide a faster and stronger immune response upon re-exposure to the same pathogen. These memory cells retain high levels of CD44 expression, distinguishing them from naive T cells. CD44 contributes to the persistence of memory T cells and their ability to quickly reactivate, potentially by increasing their responsiveness to survival signals like IL-7 and IL-15. This ability to rapidly respond is important to protective immunity, preventing recurrent infections.
CD44 T Cells in Health and Disease
CD44 T cells contribute to the body’s inflammatory responses by migrating to affected tissues. When inflammation occurs, endothelial cells in blood vessels express hyaluronic acid, which CD44 on activated T cells can bind to, facilitating their movement into the inflamed area. This directed migration helps immune cells reach sites of infection or injury.
In autoimmune diseases, the immune system mistakenly targets the body’s own tissues, and CD44 T cells can be involved. In conditions like rheumatoid arthritis or multiple sclerosis, memory CD4+ T cells that recognize self-antigens are present and contribute to tissue damage. Studies in animal models of autoimmune diseases, such as collagen-induced arthritis and autoimmune encephalomyelitis, have shown that interfering with CD44 function can reduce disease severity by limiting the migration of inflammatory cells.
In cancer, CD44 T cells can have a dual role. While T cells are recognized for their ability to fight tumors, CD44 on T cells can sometimes be manipulated by cancer cells. Some cancer cells express CD44 variants that might help them evade immune detection or promote their spread. CD44 itself is also considered a marker for cancer stem cells in various tumors, and targeting CD44 on these cells is being explored as a potential therapeutic strategy to inhibit tumor growth and spread. Understanding these roles helps in developing new treatments for immune-related diseases and cancer.