The CD4 molecule is a glycoprotein, 55-59 kDa, belonging to immunoglobulin superfamily that is associated with HLA class II antigen recognition. The epitope defines the helper-inducer subtype of T-cells. CD4 positive T cells are mainly cytokine secreting cells. The CD4 antigen is absent from immature thymocytes and is expressed during T-cell development. T-cells in thymus can simultaneously express CD4 and CD8. CD4 is also expressed on monocytes and monocyte-derived cells such as histiocytes and Langerhans cells. About 45% of peripheral blood lymphocytes are CD4-positive. In lymphatic tissuse, the CD4+ T-cells are seen in large numbers in the parafollicular zones, while scattered cells are found in the germinal centres and mantle zones. CD4 is also demonstrated in splenic littoral cells and hepatic sinusoidal cells. CD4 serves as receptor for human immunodeficiency virus (HIV). CD4 immunoreactivity using anti-Leu3a and OKT4D has been demonstrated both in normal and abnormal parathyroid glands.


Precursor T-lymphoblastic lymphomas variably express CD4. Most mature T-cell lymphomas are CD4 positive with the exception of aggressive NK-cell leukaemia and extranodal NK/T-cell lymphomas: subcutaneous panniculitis-like T-cell lymphoma (which is usually CD8 positive), enteropathy-type T-cell lymphoma and hepatosplenic T-cell lymphoma. CD4 is also expressed in histiocytic sarcomas and Langerhans cell histiocytosis as well as in splenic littoral cell haemangioma.


Classification of lymphocytes, e.g., in inflammatory lesions. Classification of malignant lymphomas (see above).


Tonsil is recommended as positive and negative tissue controls for CD4. In the tonsil, protocol must be calibrated to provide a distinct and strong membranous staining reaction in all helper/inducer T-cells. Germinal centre macrophages should at least display a moderate and distinct staining reaction. No staining reaction must be seen in other cells, including B-cells and epithelial cells of the tonsil. As a supplement to tonsil, especially in the technical calibration phase, it is recommended to verify the protocol on liver tissue. The Kupffer cells and endothelial cells in the liver sinusoids must at least display a moderate, distinct staining reaction.

Selected references

Gaubin M, Autiero M, Houlgatte R, Basmaciogullari S, Auffray C, Piatier-Tonneau D. Molecular basis of T lymphocyte CD4 antigen functions. Eur J Clin Chem Clin Biochem 1996 34:723. Kisielow P, von Boehmer H. Development and selection of T cells: facts and puzzles. Adv Immunol 1995;58:87. Mazerolles F, Auffray C, Fischer A . Downregulation of T-cell adhesion by CD4. Hum Immunol 1991;31:40. Namimatsu S, Ghazizadeh M, Sugisaki Y. J Histochem Cytochem. 2005 Jan;53(1):3-11. Reversing the effects of formalin fixation with citraconic anhydride and heat: a universal antigen retrieval method. Sattentau QJ, Weiss RA. The CD4 antigen: physiological ligand and HIV receptor. Cell 1988;52:631. Williamson SL, Steward M, Milton I, Parr A, Piggott NH, Krajewski AS, Angus B, Horne CH. New monoclonal antibodies to the T cell antigens CD4 and CD8. Production and characterization in forma-lin-fixed paraffin-embedded tissue. Am J Pathol. 1998 Jun;152(6):1421-6

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