CD4 is a glycoprotein on the surface of a subset of T-cells, which defines the T-helper subset. T-helper cells help to activate T-cell and B-cell immune response/proliferation in response to a foreign antigen. CD4 is the target/receptor of the HIV virus.
CD4 stains a subset of CD3 positive T-cells (T-helper cells). CD4 is expressed by thymocytes (80-90%), macrophages, Langerhans cells, and dendritic cells. Many T-cell leukemia/lymphomas, blastic plasmacytoid dendritic cell neoplasms, and a sub-set of AMLs will express CD4.
Negative Staining: NK cells, B-cell lymphoma, enteropathy associated T-cell lymphoma, epidermotropic cutaneous T-cell lymphoma, hepatosplenic alpha/beta and gamma/delta lymphoma, Hodgkin lymphoma, and T cell lymphoma with cytotoxic phenotype.
CD4 Expression
- Thymoctye subsets
- T-helper cells
- Monocytes
- Macrophages
- CD4+/CD56+ hematodermic neoplasm
- Dendritic cells (can express CD4 and CD8)
- T-cell Lymphomas (CD4+ more common than CD8+)
- Histiocytic disorders
- Subset of AMLs
CD4 is typically used as part of a T-cell panel to identify aberrant expression or loss of expression in cell populations of interest. Given the somewhat lack of specificity of the marker, it should be only interpreted within the context of the differential diagnosis and expected reactivity pattern(s).
By flow cytometry, low levels of CD4 expression has been demonstrated on erythroid precursor cells. This probably lacks diagnostic significance (particularly IHC), but may have implications in HIV where CD4 is the receptor the virus is mediated through.
Photomicrographs
References
Bone Marrow IHC. Torlakovic, EE, et. al. American Society for Clinical Pathology Pathology Press © 2009. pp. 24-25.
Cleveland RP, Liu YC. CD4 Expression by erythroid precursor cells in human bone marrow. Blood. 1996;87: 2275–2282.
Herling M, Jones D. CD4+/CD56+ hematodermic tumor: the features of an evolving entity and its relationship to dendritic cells. Am J Clin Pathol. 2007;127: 687–700. doi:10.1309/FY6PK436NBK0RYD4