The CD3 protein is a T-cell marker, a complex of four structurally distinct membrane glycoprotein isoforms, 20-50 kDa, comprising extracellular, transmembrane and intracellular domains. CD3 is associated with an ?/? or ?/? heterodimer creating the T-cell receptor (TCR). The CD3 complex is responsible for mediating signal transduction to the internal environment upon antigenic recognition by TCR, causing T-cell proliferation and release of cytokines. Except for a weak expression in Purkinje cells (with some of the Abs) and activated NK-cells, CD3 is found only in T-cells. CD3 appear in the cytoplasm of prothymocytes, and on the surface of about 95% of thymocytes, while cytoplasmic CD3 is lost as the cells differentiate into medullary thymocytes. In therapy resistant celiac disease, a shift from membranous to cytoplasmic CD3 expression is seen (together with loss of CD8).
In malignant lymphomas, CD3 is a pan-T-cell lineage-restricted antigen, detected in 80-97% of the T-cell lymphomas. Mature T-cell lymphomas including cases of mycosis fungoides, peripheral T-cell lymphoma and anaplastic large cell lymphoma may aberrantly lose CD3. NK-cell lymphomas can show a cytoplasmic reaction. Reed-Sternberg cells may show a globular paranuclear reaction.
CD3 is an important marker in the classification of malignant lymphomas and lymphoid leukaemias. Also the marker is useful for the identification of T-cells in, e.g., celiac disease, lymphocytic colitis and colorectal carcinomas associated with loss of a mismatch repair protein.
Tonsil is an appropriate control for CD3. Both T-cells in the interfollicular areas and dispersed T-cells in the mantle zone and within the germinal centres must show a moderate to strong distinct membranous staining reaction, while B-cells must be negative.
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