CD Markers

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CD Markers

CD3

Reviewers: Charanjeet Singh, M.D., University of Minnesota (see Reviewers page)
Revised: 18 December 2010, last major update December 2010
Copyright: (c) 2002-2010, PathologyOutlines.com, Inc.

Definition
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● Common antibody for identifying T cells

Terminology
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● Also called OKT3

Physiology
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● Member of immunoglobulin superfamily on 11q23
● Complex of delta, epsilon, gamma, zeta 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
● TCR-CD3 complex consists of either TCR alpha/beta or TCR gamma/delta heterodimers coexpressed at the cell surface with CD3

Clinical information
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● CD3 delta and epsilon defects cause autosomal recessive severe combined immunodeficiency (no T cells, normal B cells, normal NK cells, OMIM 608971, Curr Opin Allergy Clin Immunol 2004;4:479)

Anti-CD3 monoclonal antibodies, as a treatment:
● FDA approved to treat acute renal, cardiac or hepatic allograft rejection
● Improves clinical parameters in new onset type 1 diabetes (Diabetes 2005;54:1763)
● Investigational in treatment of lymphoma (Curr Drug Targets 2010;11:482) and autoimmune hepatitis (Gastroenterology 2010;139:58)
● May restore self-tolerance in autoimmune diseases (Curr Opin Immunol 2005;17:632, Ann NY Acad Sci 2004;1037:1)

Uses by pathologists
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● Most specific T cell antibody; most antibodies are directed against epsilon chain
● CD3/CD20 immunostains are often performed in the initial cytological evaluation of lymphoid-rich pleural effusions, but their cost-effectiveness has been questioned (Diagn Cytopathol 2010 Nov 22 [Epub ahead of print])

Interpretation
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● Cytoplasmic expression at early T cell differentiation, then membranous expression

Positive stains - normal
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● Thymocytes, peripheral T cells
● 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 stains - disease
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● 80% of T cell lymphomas, NK lymphoma (cytoplasmic, not membranous), lymphomatoid granulomatosis, lymphomatoid papulosis, pre T ALL (cytoplasmic staining)
● LP cells in nodular lymphocyte predominant Hodgkin's lymphoma
● Variable in primary effusion lymphoma and pyothorax associated lymphoma

Negative stains
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● Most B cell lymphomas
● Aberrant loss of CD3 in some cases of mycosis fungoides, anaplastic large cell lymphoma, angioimmunoblastic T cell lymphoma (Am J Clin Pathol 2006;126:29)
● NK large granular lymphocyte leukemia
● Reed-Sternberg cells are negative in classic Hodgkin’s lymphoma but may be surrounded by CD3 epsilon+ rosettes
● Small cell carcinoma, melanoma, granulocytic sarcoma, Ewing's sarcoma, post-transplant lymphoproliferative disorders
● Diminished expression in T cell cutaneous lymphoma (Am J Clin Pathol 2000;114:467); another study finds low CD8:CD3 ratio (< 25%) in epidermal component of lymphocytic infiltrate in these tumors (Mod Pathol 2003;16:857)

Flow cytometry
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● Adult T cell leukemia / lymphoma often has abnormally low CD3 T-cell population (Am J Clin Pathol 2005;124:199)

Micro images
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Staining of tumor cells

Natural Killer/T-Cell Lymphoma, nasal type: left - nose, right - testes-figure 3D

Hepatosplenic gamma-delta T cell lymphoma (fig A)

Breast-high grade peripheral T cell lymphoma

Nodal CD8 Positive Cytotoxic T-Cell Lymphoma

Primary effusion lymphoma-T cell type (Fig B)

Thymoma - lymphocyte predominant

Staining of nonneoplastic infiltrating T cells

Primary CNS diffuse large B cell lymphoma

Bladder: lymphoepithelioma-like carcinoma (left side)

Myeloid sarcoma - normal T cells

Nodal hamartoma - normal T cells

Halo nevus - infiltrating T cells

Inflammatory disorders - staining of T cells

Acute cellular rejection

Skin graft rejection

Intraepithelial lymphocytes in duodenum

Negative controls / no T cells identified

MALT lymphoma - negative for T cells

Virtual slides
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● Diffuse large B cell lymphoma (CD3+ reactive T cells)

Additional references
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● OMIM 186790 (CD3 delta), OMIM 186830 (CD3 epsilon), OMIM 186740 (CD3 gamma), OMIM 186780 (CD3 zeta)

End of CD Markers > CD3

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