CD4

Systemic disease: On T lymphocytes these two co-stimulatory molecules define different functional types; an altered ratio between CD4 and CD8 cells can indicate systemic disease or immune dysfunction

Neoplasia: Expanded populations of CD4 or CD8 cells (or T cells with unusual expression patterns of these molecules) may represent a malignant clone, and the CD4 or CD8 expression may help identify the disease subtype. However, restricted CD4 or CD8 expression cannot substitute for molecular clonality analysis.

Function CD4 and CD8 are transmembrane-glycoproteins that amplify signal generation by the T cell receptor. T cells acquire simultaneous expression of both CD4 and CD8 during their early the thymic stage of development, however when the mature T cells enter the circulation they express either CD4 or CD8 only. CD4 is linked to T-helper cell function, interacting with MHC class II (expressed for example on dendritic cells or B lymphocytes), but is also expressed by immune-presenting cells including monocytes, macrophages, and dendritic cells. CD8 is particularly expressed by cytotoxic cells and interacts with MHC class I (expressed on all nucleated cells) and is also expressed by natural killer cells and dendritic cells.

CD4/CD8 in health (1) CD4/CD8 ratio: for healthy individuals the ratio in blood lies between 1.5 and 2.5. An inverted ratio is considered an “immune risk” phenotype (occurring in just less than 10% of 20- to 59-year-olds but increasing with age). However, there be quite wide variation depending on a range of factors including infection with the HIV virus. (2) Absolute counts: These may be more informative than CD4/CD8 ratios: The normal CD4 count should be greater than 400/μL (reference range 500-1,500); CD8 lymphocyte counts should lie in the range to 200-800/μL

CD4/CD8 in mature T cell neoplasia (1) CD4 proliferations particularly characterise cutaneous lymphomas and T-PLL (although T-PLL may express both CD4 and CD8, or rarely only CD8) (2) CD8 proliferation typifies ATLL (although simultaneous CD4 expression may occur) and T-LGL