CD4 & CD8

Systemic disease: On T lymphocytes these two co-stimulatory molecules define different functional types of T lymphocyte; consequemtly 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 both molecules) may represent a malignant clone. The suntype of CD4 or CD8 expression may help identify the disease subtype. Restricted expression of CD4 or CD8 is not the same as molecular clonality which should be confirmed by molecular analysis.

Background

CD4 and CD8 are transmembrane-proteins that amplify signal generation by the T cell receptor. During their initial development T cells acquire simultaneous expression of both CD4 and CD8, however when the mature T cells they express only CD4 or CD8:

• CD4 is linked to T-helper cell function. It interacts 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. It interacts with MHC class I (expressed on all nucleated cells) and is also expressed by natural killer cells and dendritic cells.

Diagnostic Use

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 can be quite wide variation in this ratio depending on a range of factors that include infection (that include the HIV virus). Ratios must be interpreted in clinical context and absolute counts are preferred in many circumstances,

(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 less commonly only CD8)

(2) CD8 proliferation typifies ATLL (although simultaneous CD4 expression may occur) and T-LGL

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