CD4
Summary
CD4 is a surface glycoprotein on helper T cells that binds MHC class II and stabilizes antigen presentation. It is also the primary receptor used by HIV to enter cells, which is why the CD4 count tracks the stage of HIV disease.
Detail
CD4-positive T cells coordinate adaptive immunity: after activation they differentiate into subsets defined by cytokines and transcription factors, including Th1 (IL-12 driven, T-bet, secretes IFN-gamma, activates macrophages and cytotoxic T cells against intracellular pathogens), Th2 (IL-4 driven, GATA3, secretes IL-4, IL-5, IL-13, drives IgE and eosinophils against helminths and in atopy), Th17 (IL-17, neutrophil recruitment at mucosal surfaces), and regulatory T cells (FOXP3, IL-10 and TGF-beta, peripheral tolerance). CD4 binds the invariant beta-2 region of MHC class II, which is expressed on professional antigen-presenting cells. HIV gp120 binds CD4 and then a coreceptor, CCR5 on macrophages early in infection or CXCR4 on T cells later, and progressive CD4 depletion produces the opportunistic infections that define AIDS. Standard thresholds: below 200 cells/mm3 defines AIDS and confers risk of Pneumocystis jirovecii pneumonia, below 100 for toxoplasmosis and cryptococcus, below 50 for Mycobacterium avium complex and CMV retinitis.
Sources
- Janeway's Immunobiology
- First Aid for the USMLE Step 1
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