| First Author | Pletinckx K | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 2 | Pages | 480-91 |
| PubMed ID | 25382658 | Mgi Jnum | J:222313 |
| Mgi Id | MGI:5644353 | Doi | 10.1002/eji.201444991 |
| Citation | Pletinckx K, et al. (2015) Immature dendritic cells convert anergic nonregulatory T cells into Foxp3- IL-10+ regulatory T cells by engaging CD28 and CTLA-4. Eur J Immunol 45(2):480-91 |
| abstractText | Anergic T cells can survive for long time periods passively in a hyporesponsive state without obvious active functions. Thus, the immunological reason for their maintenance is unclear. Here, we induced peptide-specific anergy in T cells from mice by coculturing these cells with immature murine dendritic cells (DCs). We found that these anergic, nonsuppressive IL-10(-) Foxp3(-) CTLA-4(+) CD25(low) Egr2(+) T cells could be converted into suppressive IL-10(+) Foxp3(-) CTLA-4(+) CD25(high) Egr2(+) cells resembling type-1 Treg cells (Tr1) when stimulated a second time by immature DCs in vitro. Addition of TGF-beta during anergy induction favored Foxp3(+) Treg-cell induction, while TGF-beta had little effect when added to the second stimulation. Expression of both CD28 and CTLA-4 molecules on anergic T cells was required to allow their conversion into Tr1-like cells. Suppressor activity was enabled via CD28-mediated CD25 upregulation, acting as an IL-2 sink, together with a CTLA-4-mediated inhibition of NFATc1/alpha activation to shut down IL-2-mediated proliferation. Together, these data provide evidence and mechanistical insights into how persistent anergic T cells may serve as a resting memory pool for Tr1-like cells. |
