The Role of CD40-CD154 Interactions in the Regulation of Cell Mediated Immunity

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Abstract
CD40 is expressed on a diverse array of cell types from the hematopoeitic and non-hematopoeitic compartments. Within the hematopoeitic compartment, CD40 is found constitutively expressed on B cells, dendritic cells (DC) and macrophages. The function of CD40 in B cells has been documented as being essential in the control of humoral immunity. In DCs and macrophages, CD40 has been shown to be important in the induction of antigen-presenting cell (APC) maturation and effector function. CD40 is also expressed on non-hematopoeitic cells like keratinocytes, epithelial cells, and vascular endothelial cells and has been shown to be functionally important on these cell types. CD 154, the ligand for CD40, is a type II transmembrane glycoprotein of the TNF family. The human protein consists of a 22 aa cytoplasmic tail, a single 24 aa transmembrane domain and a 215 aa extracellular region (214 aa in the mouse), and human CD154 is 83% identical to murine CD154 at the nucleotide level. It is predominantly expressed on mature, activated CD4+ T cells, and can be inducibly expressed on THO, TH1 and TH2 cells. The expression of CD154 is tightly regulated, peaking 6–8 hr. postactivation in vitro and returning to resting levels by 24–48 hr. In addition to CD4+ T cells, CD 154 is reportedly found in a small population of activated CD8-t T cells, purified NK cells, monocytes, basophils, mast cells, activated eosinophils, and platelets. As one might expect due to the wide distribution of both the receptor and its ligand, especially on highly proliferative cells and antigen presenting cells, CD40-CD154 interactions have a very broad physiological role in the regulation of immune responses, as reviewed (1,2).