CD4

Also called OKT4

Nonpolymorphous glycoproteins belonging to immunoglobulin superfamily

Expressed on surface of T helper cells; serves as coreceptor in MHC class II-restricted antigen induced T cell activation

CD4+ CD25+ T cells maintain peripheral tolerance and prevent autoimmunity (Curr Top Microbiol Immunol 2005;293:115)

Serves as HIV receptor on T cells, macrophages, brain

Downregulated by HIV Nef protein during AIDS progression (J Virol 2003;77:11536, J Biol Chem 2003;278:33912)

Normally CD4 > CD8; in HIV patients, CD4/CD8 ratio is inverted (i.e. CD4 < CD8) and patients are at risk for opportunistic infections

Homologous to CD223

Uses: classify lymphomas and inflammatory conditions; serum levels are marker of HIV disease progression and response to therapy (CD4+ cells are killed by HIV); serum levels also increased by transient stress (AJCP 2002;117:819)

Drawings: (1) CD4+ T cell and antigen presenting cell; (2) HIV entry into T cells

Positive staining (normal): thymocytes (80-90%), T helper cells, macrophages, Langerhans cells, dendritic cells, granulocytes

Positive staining (disease): many post-thymic T cell leukemia/lymphomas, indolent T cell lymphoblastic proliferation, pityriasis lichenoides, CD4+ CD56+ hematodermic malignancies (blastic NK lymphoma), histiocytic lymphoma / sarcoma, acute myeloid leukemia (AJCP 1995;104:204), some pyothorax associated lymphomas, cutaneous lymphomatoid granulomatosis (AJSP 2001;25:1111), lymphomatoid papulosis (variable), florid antiviral inflammatory response (Mod Path 2003;16:166)

Negative staining: NK cells, T cell lymphoma with cytotoxic phenotype, hepatosplenic alpha/beta and gamma/delta lymphoma, enteropathy associated T cell lymphoma, B cell lymphoma (usually), Hodgkin’s lymphoma (usually), nonhematopoietic neoplasms

References: Cell 1985;42:93 (early article), OMIM 186940