CD28 costimulation: from mechanism to therapy

By Jonathan H. Esensten, Ynes A. Helou, G. Chopra, A. Weiss, J. Bluestone. Immunity, 2016

817 citations recorded by the source corpus.

Summary Ligation of the CD28 receptor on T cells provides a critical second signal alongside T cell receptor (TCR) ligation for naive T cell activation. Here we discuss the expression, structure, and biochemistry of CD28 and its ligands. CD28 signals play a key role in many T cell processes including cytoskeletal remodeling, production of cytokines, survival, and differentiation. CD28 ligation leads to unique epigenetic, transcriptional, and post-translational changes in T cells that cannot be recapitulated by TCR ligation alone. We discuss the function of CD28 and its ligands in both effector and regulatory T cells. CD28 is critical for regulatory T cell survival and the maintenance of immune homeostasis. We outline the roles that CD28 and its family members play in human disease and we review the clinical efficacy of drugs that block CD28 ligands. Despite the centrality of CD28 and its family members and ligands to immune function, many aspects of CD28 biology remain unclear. Translation of a basic understanding of CD28 function into immunomodulatory therapeutics has been uneven with both successes and failures. Such real-world results may stem from multiple factors including complex receptor-ligand interactions among CD28 family members, differences between the mouse and human CD28 families, and cell-type specific roles of CD28 family members.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/38077f94b0c56dd724c6a9ab4cab1a086497bb27

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Rafi Ahmed
2. Arlene H. Sharpe
3. G. Freeman
4. K. Araki
5. G. Lee
6. B. Blazar
7. Erika L. Pearce
8. E. Wherry

Citations in the corpus

• The Balance of Th17 versus Treg Cells in Autoimmunity (2018, background): “When the TCR, together with co-receptors CD4 or CD8, binds to the peptide–MHC complex on the surface of APCs, the immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic tails of the CD3 chains are located in close proximity to protein kinase Lck, which is associated with the cyto”
• Unraveling the Complex Interplay Between T Cell Metabolism and Function (2018, background): “In a proinflammatory environment, TCR signals along with costimulation lead to a growth phase in which T cells augment global metabolism (21, 22), a process dependent on phosphoinositide-3 kinase (PI3K)/AKT/mTOR signals (10, 23).”
• Rescue of exhausted CD8 T cells by PD-1 targeted therapies is CD28-dependent (2017, background): “CD28 engagement reduces T cell receptor signaling threshold required for T cell activation, and may provide qualitatively different signals (5).”