CD28 family receptor

CD28 family receptors are a group of regulatory cell surface receptors expressed on immune cells. The CD28 family in turn is a subgroup of the immunoglobulin superfamily.^[1]

Two family members, CD28 and ICOS, act as positive regulators of T cell function while another three, BTLA,^[2]CTLA-4 and PD-1 act as inhibitors.^[1] Ligands for the CD28 receptor family include B7 family proteins.^[3]

CD28 receptors play a role in the development and proliferation of T cells.^[4] The CD28 receptors enhance signals from the T cell receptors (TCR) in order to stimulate an immune response^[5] and an anti-inflammatory response on regulatory T cells. Through the promotion of T cell function, CD28 receptors allow effector T cells to combat regulatory T cell-mediated suppression from adaptive immunity. CD28 receptors also elicit the prevention of spontaneous autoimmunity.

CD28 receptors aid in other T cell processes such as cytoskeletal remodeling, production of cytokines and chemokines and intracellular biochemical reactions (i.e. phosphorylation, transcriptional signaling, and metabolism) that are key for T cell proliferation and differentiation. Ligation of CD28 receptors causes epigenetic, transcriptional and post-translational alterations in T cells. Specifically, CD28 costimulation controls many aspects within T cells, one being the expression of proinflammatory cytokine genes. A particular cytokine gene encodes for IL-2, which influences T cell proliferation, survival, and differentiation. The absence of CD28 costimulation results in the loss of IL-2 production causing the T cells to be anergic.^[6] Additionally, CD28 ligation causes arginine-methylation for many proteins. CD28 also drives transcription within T cells and produce signals that lead to IL-2 production and Bcl-xL regulation, an antiapoptotic protein, which are essential for T cell survival.^[7] CD28 receptors can be seen on 80% of human CD4+ and 50% of CD8+ T cells, in which this percentage decreases with age.^[8]