| First Author | Shameli A | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 2 | Pages | 394-403 |
| PubMed ID | 23180662 | Mgi Jnum | J:192807 |
| Mgi Id | MGI:5466607 | Doi | 10.1002/eji.201242845 |
| Citation | Shameli A, et al. (2013) IL-2 promotes the function of memory-like autoregulatory CD8(+) T cells but suppresses their development via FoxP3(+) Treg cells. Eur J Immunol 43(2):394-403 |
| abstractText | 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-2Rbeta (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. |
