Review ArticleRoles of CD48 in regulating immunity and tolerance

•CD48 is constitutively expressed on hematopoietic cells and upregulated on subsets during allergy, infection and malignancy•CD48:CD2 interactions promote immune synapse organization, adhesion, and TCR signaling•CD48:CD244 interactions control NK and CTL activation and cytolytic function•Multiple studies suggest that CD48 and CD58 are valuable therapeutic targets in human disease

CD48, a member of the signaling lymphocyte activation molecule family, participates in adhesion and activation of immune cells. Although constitutively expressed on most hematopoietic cells, CD48 is upregulated on subsets of activated cells. CD48 can have activating roles on T cells, antigen presenting cells and granulocytes, by binding to CD2 or bacterial FimH, and through cell intrinsic effects. Interactions between CD48 and its high affinity ligand CD244 are more complex, with both stimulatory and inhibitory outcomes. CD244:CD48 interactions regulate target cell lysis by NK cells and CTLs, which are important for viral clearance and regulation of effector/memory T cell generation and survival. Here we review roles of CD48 in infection, tolerance, autoimmunity, and allergy, as well as the tools used to investigate this receptor. We discuss stimulatory and regulatory roles for CD48, its potential as a therapeutic target in human disease, and current challenges to investigation of this immunoregulatory receptor.