CD7-

Synonyms: Cluster of differentiation 7

by Assia Bassarova

Background

Human CD7 is a member of the immunoglobulin (Ig) superfamily. The human CD7 gene is located on chromosome 17q25.2-25.3. The CD7 polypeptide is a protein of 240 amino acids with the characteristics of an integral membrane protein. CD7 molecule is a 40 kDa single-chain Ig molecule, expressed on most thymocytes, on the surface of peripheral blood T lymphocytes, and NK cells. It is also expressed early in hematopoietic cell ontogeny on B- and myeloid cells. CD7 ligand, SECTM1/K12, is produced by cells of the human thymic microenvironment including epithelial cells and fibroblasts, breast cancer and leukemia cell lines, and neutrophils but not in peripheral lymphocytes. The expression of SECTM1 can be up-regulated by IFN-γ in many cell types, including thymic epithelial cells and monocytes. CD7 is expressed early in T-cell development and is suggested to be an early marker of T-cell precursors in the T-cell lineage. It has been shown that CD7 is not exclusively a T-cell lineage-commitment marker. It is postulated that CD7 is an early cell-surface marker of a pluripotent progenitor cells capable to differentiate into both T-, B- and myeloid lineages. However, both B cells and myeloid cells normally lose CD7 expression during maturation.

Staining in normal cells/tissues: CD7 is expressed early in lymphocyte and myeloid development and in mature human T- and NK cells. The majority of mature CD4+ and CD8+ peripheral T cells express CD7. There are, however, small subsets of T cells lacking CD7 on the cell surface. A small population of CD4+CD45RA–CD45RO+ memory T cells that lose CD7 expression has been defined in normal human blood. In addition, a small population of CD7+CD3– cells were identified in the peripheral blood of normal adult donors. These cells were apparently distinct from NK cells being able to differentiate into CD3+ T cells upon stimulation.

The percentages and absolute numbers of CD7- T cells in peripheral blood increase significantly during aging. An absence of CD7 antigen expression on T cells is observed in different pathologic conditions. Specific absence of this antigen in T cells is associated with severe combined immunodeficiency. Benign and malignant skin diseases, HIV infection, rheumatoid arthritis, and kidney transplantation are associated with an increase in the CD7– T cell subpopulation.

Staining in tumors: As an immunohistochemical marker both the expression and loss of expression of CD7 are clinically significant.

  • (+) Most of precursor T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-cell ALL/LBL) (Fig. 2), in thymomas (showing heterogeneous expression) (Fig. 3), enteropathy-associated T-cell lymphoma (EATL) type II, epidermotropic CD8+ cytotoxic T cell lymphoma.
  • (+/-) Peripheral T-cell lymphoma, NOS, angioimmunoblastic T-cell lymphoma (Fig. 4), aberrant expression of the CD7 in AML and transient myeloproliferative disorders in Down syndrome.
  • (-/+) Discoordinated expression of the intraepidermal and dermal neoplastic T-cells in mycosis fungoides (MF); CD7 expression in a proportion of non-hematopoietic neoplasms, in particular in cholangiocarcinoma, pancreatic ductal carcinoma, lung and ovarian adenocarcinoma, malignant melanoma and epithelioid sarcoma.
  • -(+) In some rare B-cell lymphoma cases with aberrant expression of T-cell markers.
  •  [-] B-cell ALL/LBL, characteristically absent in the circulating Sezary cells in the peripheral blood from patients with Sezary syndrome.

Staining pattern: Distinct membranous and cytoplasmic staining.

Control tissue: Normal tonsil and normal appendix show moderate to strong staining in the perifollicular (T-cell) areas as well as single spread small T-cells in the germinal centers and mantle/marginal zones of the B-follicles.

Application:

  • Discriminating refractory celiac disease cases with CD7 positive IELs from early EATL where IELs are CD7 negative
  • Sub-classifying EATL into type I and type II.
  • Discriminating reactive skin lymphoid infiltrates from early MF.
  • Positive expression is a negative prognostic marker in myeloid malignancies and epidermotropic CD8+ cytotoxic T cell lymphoma
  • Loss of expression is a negative prognostic marker in acute myelogenous leukemia with FLT3/ITD and aggressive NK cell lymphoma

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