CD 4

Ancell (QS4120), Becton Dickinson (Leu3), Biodesign (13B8.2, BL4), Biogenesis (T138A), Biotest (T4, TT1), Coulter (T4), Cymbus Bioscience (MEM115), Dako (MT310), GenTrak, Immunotech (BL4, 13B8.2), Oncogene (VIT4), Sanbio (BL-TH4), MEM115), Seralab, Serotec (B-A1, B-F5, B-B14, 13B8.2) and Pharmingen (RM-4-4, RM-4-5).

Fresh-frozen tissue and cell preparations.

After the discovery that lymphocytes could be divided into B cells and T-cells, discrete subsets of T-cells which function as helper, suppressor and cytotoxic cells were recognized. The CD 4 molecule is a non-polymorphic glycoprotein belonging to the Ig gene superfamily that is expressed on the surface membrane of functionally distinct subpopulation of T cells, mutually exclusive of the CD 8 molecule (Maddon et al, 1985). The CD4 molecule is a 55 kD glycoprotein with five external domains, each homologous to an Ig light chain-variable region, a transmembrane domain and a highly conserved intracellular domain. The CD 4 gene has been mapped to the short arm of chromosome 12 (Isobe et al, 1986; Brady & Barclay, 1996).
The CD 4 molecule acts as a coreceptor with the TCR complex and appears to bind to the non-polymorphic region of the MHC class II molecule and may serve to increase the avidity of cell-to-cell interactions. It also serves as a receptor for the human immunodeficiency virus on T-cells, monocytes/macrophages and in some neural cells (Dalgleish et al, 1984; Doyle & Strominger, 1987).
The CD 4 antigen, like CD 8, appears at the common thymocyte stage of T-cell differentiation and is expressed in about 80-90% of normal thymocytes. CD 4 thus marks helper/inducer T-cells and is expressed in 55-65% of mature peripheral T-cells. It should be noted that the phenotype-functional association of CD 4 to helper and CD 8 to suppressor/cytotoxic function is not universal. Subpopulations of suppressor or cytotoxic T cells can be identified among CD 4+ T-cells. Although also expressed on monocytes/macrophages, Langerhans cells and other dendritic cells, CD 4 is not expressed by B cells.

The CD 4 antibody is useful for the identification of T helper/inducer cells and plays an important role in the immunophenotyping of reactive lymphocytes and in lymphoproliferative disorders. The majority of peripheral T-cell lymphomas are derived from the helper T-cell subset so that most postthymic T-cell neoplasms are CD 4+CD 8-. Tg-lymphoproliferative disease is an exception where the proliferative cells are CD 4-CD 8+. As with other T-cell antigens, CD 4 may be aberrantly deleted in neoplastic T-cells so that the evaluation of such tumors requires the application of a panel of markers in order to identify tumors with such anomalous antigenic expression.

Current anti-CD 4 antibodies are immunoreactive only in fresh-frozen tissue sections and fresh cytologic preparations. In the latter preparations, fixation in 10% buffered formalin or in 0.1% formal saline produces consistent immunostaining especially if heat-induced epitope retrieval is employed. There is satisfactory staining of reactive T-cells in paraffin-embedded sections following heat-induced epitope retrieval but the staining is weak in neoplastic T-cells. Many phagocytic histiocytes and dendritic cells are also CD 4+, making interpretation of frozen section staining difficult. OPD4 (CD45RA) was initially claimed to be specific for CD 4+ T-cells, but this has not been proven to be so and OPD4 labels both CD 4+ and CD 8+ cells.

•Brady RL, Barclay AN 1996. The structure of CD4. Current Topics in Microbiology and Immunology 205: 1-18.

•Dalgleish AG, Beverley PLC, Clamham PR et al 1984. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312: 763-766.

•Doyle C, Strominger JL 1987. Interaction between CD4 and Class II MHC molecules mediates cell adhesion. Nature 330: 256-259.

•Isobe M, Huebner K, Maddon PJ et al 1986. The gene encoding the T cell surface protein T4 is located on human chromosome 12. Proceedings of the National Academy of Science USA 83: 4399-4402.

•Maddon PJ, Littman DR, Godfrey M et al 1985. The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family. Cell 42: 93-104.

Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.