Table of Contents
Definition / general | Pathophysiology | Clinical features | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Flow cytometry description | Flow cytometry imagesCite this page: Pernick N. CD3. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd3.html. Accessed January 24th, 2021.
Definition / general
- Common antibody for identifying T cells
- Member of immunoglobulin superfamily on 11q23
- Also called OKT3
Pathophysiology
- Complex of delta (CD3d, OMIM #186790), epsilon (CD3e, OMIM #186830), gamma (CD3g, OMIM #186740), zeta (OMIM #186780, also called CD247) and eta chains of integral membrane glycoproteins that associates with T cell antigen receptor (TCR), and is required for TCR cell surface expression and signal transduction (see Lymph nodes-not lymphoma chapter)
- TCR-CD3 complex consists of either TCR alpha / beta or TCR gamma / delta heterodimers coexpressed at cell surface with CD3
Clinical features
- CD3 gamma (Pediatr Allergy Immunol 2013;24:257), delta and epsilon defects cause autosomal recessive severe combined immunodeficiency (no T cells, normal B cells and normal NK cells, OMIM #608971, Curr Opin Allergy Clin Immunol 2004;4:479)
Anti-CD3 monoclonal antibodies as treatment: - FDA approved to treat acute renal, cardiac or hepatic allograft rejection (MAbs 2010;2:148)
- Deplete T cells from donor marrow prior to transplant
- Reverse steroid-resistant acute graft rejection (J Immunol 2011;187:2015)
- Although initially thought to improve clinical parameters in new onset type 1 diabetes (N Engl J Med 2002;346:1692, Diabetes 2005;54:1763), phase III trials have been disappointing (Clin Dev Immunol 2011;2011:432016)
Uses by pathologists
- Most specific T cell antibody; usually to identify T cells in benign and malignant disorders; most antibodies are directed against epsilon chain
- CD3 / CD20 immunostains are often performed in initial cytological evaluation of lymphoid-rich pleural effusions, but their cost-effectiveness has been questioned (Diagn Cytopathol 2012;40:565)
- Does NOT improve detection of gluten sensitive enteropathy when H&E sections are normal.(Mod Pathol 2013;26:1241)
Microscopic (histologic) images
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Cases of the month
Staining of tumor cells:
Staining of nonneoplastic infiltrating T cells:
Negative controls / no T cells identified:
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Staining of tumor cells:
Staining of nonneoplastic infiltrating T cells:
Inflammatory disorders - staining of T cells:
Negative controls / no T cells identified:
Positive staining - normal
- Thymocytes, peripheral T cells (cytoplasmic expression at early T cell differentiation, then membranous expression)
- NK cells (CD3 epsilon, cytoplasmic in 56%, not membranous); also Purkinje cells of cerebellum
- Note: nonspecific cytoplasmic staining may be present in plasma cells and macrophages
Positive staining - disease
- Polykaryocytes in various benign and malignant disorders
- 80% of T cell lymphomas, NK lymphoma (cytoplasmic, not membranous), lymphomatoid granulomatosis, lymphomatoid papulosis and pre T ALL (cytoplasmic staining)
- LP cells in nodular lymphocyte predominant Hodgkin lymphoma
- Variable in primary effusion lymphoma and pyothorax associated lymphoma
Negative staining
- B cells, histiocytes and histiocytic lesions, osteoblasts
- Most B cell lymphomas, but aberrant staining exists (Am J Surg Pathol 2012;36:1364)
- Aberrant loss of CD3 in some cases of mycosis fungoides (Am J Clin Pathol 2000;114:467), anaplastic large cell lymphoma and angioimmunoblastic T cell lymphoma (Am J Clin Pathol 2006;126:29)
- NK large granular lymphocyte leukemia
- Reed-Sternberg cells are negative in classic Hodgkin lymphoma but may be surrounded by CD3 epsilon+ rosettes; LP cells in nodular lymphocyte predominant Hodgkin lymphoma are CD3-
- Small cell carcinoma, melanoma, granulocytic sarcoma, Ewing sarcoma and post-transplant lymphoproliferative disorders
Flow cytometry description
- Adult T cell leukemia / lymphoma often has abnormally low CD3 T cell population (Am J Clin Pathol 2005;124:199, Virol J 2007;4:85)