Soluble CD25 imposes a low-zone IL-2 signaling environment that favors competitive outgrowth of antigen-experienced CD25 high regulatory and memory T cells.

Autor: Nickle RA; Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA. Electronic address: rebecca.nickle@biolegend.com., DeOca KB; Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA. Electronic address: kayla.b.deoca@gmail.com., Garcia BL; Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA. Electronic address: garciabr18@ecu.edu., Mannie MD; Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, USA. Electronic address: manniem@ecu.edu.
Jazyk: angličtina
Zdroj: Cellular immunology [Cell Immunol] 2023 Feb; Vol. 384, pp. 104664. Date of Electronic Publication: 2023 Jan 05.
DOI: 10.1016/j.cellimm.2023.104664
Abstrakt: 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, IL2Rβγ, and IL2Rαβγ 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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