title: The story of CD4+ CD28- T cells revisited: solved or still ongoing?
abstract: 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.
authors.affiliation: Clinic VI, Laboratory of Molecular Biology and Rheumatology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Maly
authors.affiliation: Clinic VI, Laboratory of Molecular Biology and Rheumatology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Michael
authors.identifier: 0000-0001-9208-7809
authors.initials: M
authors.lastname: Schirmer
mesh_terms: D018106:CD28 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016922:Cellular Senescence; D060965:Clonal Evolution; D004198:Disease Susceptibility / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018655:Lymphocyte Count; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018106:CD28 Antigens
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