CD4

Characteristics

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 (Fig 1a), 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.

Neoplasms

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 (Fig 1b).

Application

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

Visualization

The antibodies available for paraffin sections are not as sensitive as those for flow cytometry and frozen sections. For paraffin sections, clones 1F6 and 4B12 are appropriate. Heat induced epitope retrieval is mandatory. As regards clone 1F6, according to vendor recommendations, blocking of endogenous peroxidase in >1 % H2O2 after HIER can be deteriorative to the antigen detected. This has been confirmed in several NordiQC reference laboratories. Thus it is recommended either to use a lower concentration of H2O2, performing the peroxidase blocking before HIER or omit endogenous peroxidase blocking at all.

Control tissue: tonsil. Compared to normal helper/inducer T-cells the macrophages generally express a weak CD4 staining. The capability to detect these cells verifies the sensitivity of the used protocol.

Assessments

Run 14 2005

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