| First Author | Elizondo DM | Year | 2019 |
| Journal | J Leukoc Biol | Volume | 105 |
| Issue | 1 | Pages | 123-130 |
| PubMed ID | 30512224 | Mgi Jnum | J:268945 |
| Mgi Id | MGI:6272048 | Doi | 10.1002/JLB.1A0118-010RR |
| Citation | Elizondo DM, et al. (2019) IL-10 producing CD8(+) CD122(+) PD-1(+) regulatory T cells are expanded by dendritic cells silenced for Allograft Inflammatory Factor-1. J Leukoc Biol 105(1):123-130 |
| abstractText | Allograft Inflammatory Factor-1 (AIF1) is a cytoplasmic scaffold protein that contains Ca(2+) binding EF-hand and PDZ interaction domains important for mediating intracellular signaling complexes in immune cells. The protein plays a dominant role in both macrophage- and dendritic cell (DC)-mediated inflammatory responses. This study now reports that AIF1 expression in DC is important in directing CD8(+) T cell effector responses. Silencing AIF1 expression in murine CD11c(+) DC suppressed antigen-specific CD8(+) T cell activation, marked by reduced CXCR3, IFNgamma and Granzyme B expression, and restrained proliferation. These primed CD8(+) T cells had impaired cytotoxic killing of target cells in vitro. In turn, studies identified that AIF1 silencing in DC robustly expanded IL-10 producing CD8(+) CD122(+) PD-1(+) regulatory T cells that suppressed neighboring immune effector responses through both IL-10 and PD-1-dependent mechanisms. In vivo studies recapitulated bystander suppression of antigen-responsive CD4(+) T cells by the CD8(+) Tregs expanded from the AIF1 silenced DC. These studies further demonstrate that AIF1 expression in DC serves as a potent governor of cognate T cell responses and present a novel target for engineering tolerogenic DC-based immunotherapies. |
