What is the significance of CD2, CD3, CD7, CD45, CD56, and T-cell receptor (TcR) expression in immunophenotyping?

From the Guidelines

The expression of CD2, CD3, CD7, CD45, CD56, and T-cell receptor (TcR) is crucial in immunophenotyping for distinguishing between different types of lymphomas and leukemias, with CD3 and TcR being specific to T lymphocytes, as noted in the 2022 NCCN clinical practice guidelines in oncology 1. The significance of these markers lies in their ability to identify and characterize immune cells, particularly lymphocytes. CD3 and TcR are essential for T cell activation and signaling, with CD3 being a co-receptor that associates with the TcR to form the TCR complex. CD2, expressed on T cells and natural killer (NK) cells, functions as an adhesion molecule, facilitating cell-cell interactions. CD7, found on T cells and NK cells early in their development, plays a role in T cell activation and interaction with other immune cells. CD45, a protein tyrosine phosphatase, is critical for signal transduction in immune responses and is found on all leukocytes. CD56, primarily expressed on NK cells and some T cell subsets, serves as a marker for these populations.

Key points about these markers include:

• CD3 and TcR are specific to T lymphocytes and are used to identify T-cell lymphomas, such as PTCL-NOS, which often express CD4 and lack CD8, although variations exist 1.
• CD2, CD7, and CD56 can be used to distinguish between different subtypes of T-cell lymphomas, with AITL cells typically expressing CD4 and T-cell–associated antigens 1.
• CD45 is a useful marker in flow cytometry for identifying leukocytes and can be used in conjunction with other markers to diagnose hematologic malignancies 1.
• The absence or abnormal expression of these markers can indicate specific disease states, such as certain types of leukemias or lymphomas, highlighting the importance of adequate immunophenotyping in diagnosis and treatment planning 1.

From the Research

Significance of CD2, CD3, CD7, CD45, CD56, and T-cell receptor (TcR) expression

• CD2, CD3, CD7, CD45, CD56, and TcR are surface markers that play crucial roles in immunophenotyping, which is the process of identifying and characterizing immune cells based on their surface proteins 2, 3, 4.
• The T-cell receptor (TcR) is a specific surface marker for T cells, and it regulates T cell function and participates in the body's immunological response to prevent immune dysregulation and inflammatory reactions by identifying and binding exogenous antigens 2.
• The CD3 molecule is essential for TCR structural stability and T cell activation signaling, and a TCR-CD3 complex is created when TCR and CD3 form a non-covalent bond, facilitating antigen recognition and T cell signaling 2, 5.
• CD2 and CD7 are also important surface markers for T cells, and their expression can vary between different T cell subsets, with CD4+ T cells exhibiting higher CD3 antigen expression compared to CD8+ T cells 3, 4.
• CD45 is a surface marker that is expressed on all leukocytes, including T cells, and it plays a role in T cell activation and signaling 4.
• CD56 is a surface marker that is typically associated with natural killer (NK) cells, but it can also be expressed on a subset of T cells, known as CD56+ T cells, which have been shown to have potential for immunotherapy as antitumor cytotoxic effectors 6.
• The expression of these surface markers can be used to identify and characterize different T cell subsets, and to understand their functions and roles in the immune response 3, 4, 6.

Expression of CD2, CD3, CD7, CD45, CD56, and TcR on T cell subsets

• CD4+ T cells express higher levels of CD3 and CD2 compared to CD8+ T cells 3, 4.
• CD8+ T cells express higher levels of CD7 compared to CD4+ T cells 3.
• CD56+ T cells express higher levels of CD56 and lower levels of CD2 and CD5 compared to CD56- T cells 6.
• The expression of these surface markers can vary between different T cell subsets, and can be used to identify and characterize these subsets 3, 4, 6.

Clinical significance of CD2, CD3, CD7, CD45, CD56, and TcR expression

• The expression of these surface markers can be used to diagnose and monitor immune-related diseases, such as autoimmune diseases and immunodeficiencies 2, 3, 4.
• CD56+ T cells have been shown to have potential for immunotherapy as antitumor cytotoxic effectors, and their expression of CD56 and other surface markers can be used to identify and characterize these cells 6.
• The expression of these surface markers can also be used to monitor the response to immunotherapy and to identify potential targets for immunomodulatory drugs 5, 6.