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- Title
IL-2 promotes the function of memory-like autoregulatory CD8<sup>+</sup> T cells but suppresses their development via Fox P3<sup>+</sup> Treg cells.
- Authors
Shameli, Afshin; Yamanouchi, Jun; Tsai, Sue; Yang, Yang; Clemente‐Casares, Xavier; Moore, Anna; Serra, Pau; Santamaria, Pere
- Abstract
IL-2 plays a critical role in both effector T-cell development and Fox P3+ CD4+ Treg-cell homeostasis. A reduction in Il2 transcription results in impaired Fox P3+ CD4+ Treg-cell recruitment and function, and accounts for the association between murine Il2 and type 1 diabetes ( T1 D). The progression of T1 D 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-2 Rβ ( 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 Fox P3+ Treg cells in nonobese diabetic mice. These results illustrate a complex homeostatic interplay between IL-2, CD4+ Th cells, Fox P3+ 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 Fox P3+ CD4+ Treg-cell function results in the suppression of CD4+ Th-cell activation and autoregulatory memory CD8+ T-cell formation.
- Publication
European Journal of Immunology, 2013, Vol 43, Issue 2, p394
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201242845