| First Author | Nickle RA | Year | 2023 |
| Journal | Cell Immunol | Volume | 384 |
| Pages | 104664 | PubMed ID | 36642016 |
| Mgi Jnum | J:351192 | Mgi Id | MGI:7433962 |
| Doi | 10.1016/j.cellimm.2023.104664 | Citation | Nickle RA, et al. (2023) Soluble CD25 imposes a low-zone IL-2 signaling environment that favors competitive outgrowth of antigen-experienced CD25(high) regulatory and memory T cells. Cell Immunol 384:104664 |
| abstractText | This study focused on soluble (s)CD25-mediated regulation of IL-2 signaling in murine and human CD4(+) T cells. Recombinant sCD25 reversibly sequestered IL-2 to limit acute maximal proliferative responses while preserving IL-2 bioavailability to subsequently maintain low-zone IL-2 signaling during prolonged culture. By inhibiting IL-2 signaling during acute activation, sCD25 suppressed T-cell growth and inhibited IL-2-evoked transmembrane CD25 expression, thereby resulting in lower prevalence of CD25(high) T cells. By inhibiting IL-2 signaling during quiescent IL-2-mediated growth, sCD25 competed with transmembrane CD25, IL2Rbetagamma, and IL2Ralphabetagamma receptors for limited pools of IL-2 such that sCD25 exhibited strong or weak inhibitory efficacy in IL-2-stimulated cultures of CD25(low) or CD25(high) T cells, respectively. Preferential blocking of IL-2 signaling in CD25(low) but not CD25(high) T cells caused competitive enrichment of CD25(high) memory/effector and regulatory FOXP3(+) subsets. In conclusion, sCD25 modulates IL-2 bioavailability to limit CD25 expression during acute activation while enhancing CD25(high)T-cell dominance during low-zone homeostatic IL-2-mediated expansion, thereby 'flattening' the inflammatory curve over time. |
