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Journal of Immunology Research
Volume 2015, Article ID 348746, 11 pages
Review Article

The Story of CD4+CD28 T Cells Revisited: Solved or Still Ongoing?

Clinic VI, Laboratory of Molecular Biology and Rheumatology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria

Received 29 November 2014; Revised 10 February 2015; Accepted 19 February 2015

Academic Editor: Peirong Jiao

Copyright © 2015 Kathrin Maly and Michael Schirmer. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.