The story of CD4+CD28- T cells revisited: Solved or still ongoing?

Cd4+cd28- t cells are a unique type of proinflammatory t cells characterised by blockade of costimulatory cd28 receptor expression at the transcriptional level,which is still reversible by il-12. in healthy individuals older than 65 years,these cells may accumulate to up to 50% of total cd4+ t lymphocytes as in many immune-mediated diseases,immunodeficiency,and specific infectious diseases. here we focus on cd4+cd28- t cells in chronic immune-mediated diseases,summarizing various phenotypic and functional characteristics,which vary depending on the underlying disease,disease activity,and concurrent treatment. cd4+cd28- t cells present as effector/memory cells with increased replicative history and oligoclonality but reduced apoptosis. as an alternative costimulatory signal instead of cd28,not only natural killer cell receptors and toll-like receptors,but also cd47,ctla-4,ox40,and 4-1bb have to be considered. the proinflammatory and cytotoxic capacities of these cells indicate an involvement in progression and maintenance of chronic immune-mediated disease. so far it has been shown that treatment with tnf-α blockers,abatacept,statins,and polyclonal antilymphocyte globulins (atg) mediates reduction of the cd4+cd28- t cell level. the clinical relevance of targeting cd4+cd28- t cells as a therapeutic option has not been examined so far. © 2015 kathrin maly and michael schirmer.