[{"titleInfo":{"title":"IL-2 promotes the function of memory-like autoregulatory CD8+ T cells but suppresses their development via FoxP3+ Treg cells"},"name":[{"type":"personal","given":["Afshin"],"family":["Shameli"]},{"type":"personal","given":["Jun"],"family":["Yamanouchi"]},{"type":"personal","given":["Sue"],"family":["Tsai"]},{"type":"personal","given":["Yang"],"family":["Yang"]},{"type":"personal","given":["Xavier"],"family":["Clemente-Casares"]},{"type":"personal","given":["Anna"],"family":["Moore"]},{"type":"personal","given":["Pau"],"family":["Serra"]},{"type":"personal","given":["Pere"],"family":["Santamaria"]}],"typeOfResource":"text","abstract":"IL-2 plays a critical role in both effector T-cell development and FoxP3(+) CD4(+) Treg-cell homeostasis. A reduction in Il2 transcription results in impaired FoxP3(+) CD4(+) Treg-cell recruitment and function, and accounts for the association between murine Il2 and type 1 diabetes (T1D). The progression of T1D elicits a disease-countering negative feedback regulatory loop that involves the differentiation of low-avidity autoreactive CD8(+) T cells into memory-like autoregulatory T cells in a CD4(+) Th-dependent manner. Since these auto-regulatory T cells express IL-2R\u03b2 (CD122), we hypothesized that their development might also be regulated by IL-2. Here, we investigate the effects of differences in IL-2 expression on this autoregulatory subset. We show that decreased IL-2 production impairs the regulatory capacity of memory-like autoregulatory CD8(+) CD122(+) T cells. Surprisingly, we also find that a reduction in IL-2 production capacity increases memory autoregulatory CD8(+) T-cell formation indirectly, by decreasing the development and function of FoxP3(+) Treg cells in nonobese diabetic mice. These results illustrate a complex homeostatic interplay between IL-2, CD4(+) Th cells, FoxP3(+) CD4(+) Treg cells and autoregulatory CD8(+) T-cell memory whereby IL-2 controls the function of both Treg-cell subsets, but IL-2-potentiation of FoxP3(+) CD4(+) Treg-cell function results in the suppression of CD4(+) Th-cell activation and autoregulatory memory CD8(+) T-cell formation.","identifier":{"citekey":"Shameli2013","doi":"10.1002\/eji.201242845","pubmed":"23180662"},"host":{"titleInfo":{"full":"European journal of immunology","abbreviated":"Eur. J. Immunol"},"genre":{"marcgt":"periodical","nlm":"academic journal"},"language":"eng","identifier":{"issn":"1521-4141"},"part":{"date":"2013 Feb 15","detail":{"volume":"43","issue":"2","page":"394-403"},"extent":{"page":{"start":"394","end":"403"}}}}}]