Allogeneic cord blood regulatory T cells can resolve lung inflammation

Mi Ae Lyu, Meixian Huang, Ke Zeng, Li Li, Joseph D. Khoury, Mitsutaka Nishimoto, Hongbing Ma, Tara Sadeghi, Siddhartha Mukherjee, Arthur S. Slutsky, Christopher R. Flowers, Simrit Parmar

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background aims: CD4+CD25+CD127lo regulatory T cells (Tregs) are responsible for maintaining immune homeostasis. Tregs can be rendered defective and deficient as a result of the immune imbalance seen in lung injury, and such dysfunction can play a major role in continued tissue inflammation. The authors hypothesized that adoptive therapy with healthy allogeneic umbilical cord blood (UCB)-derived Tregs may be able to resolve inflammation. Results: Ex vivo-expanded UCB Tregs exhibited a unique phenotype with co-expression of CD45RA+CD45RO+ >80% and lung homing markers, including CD49d. UCB Tregs did not turn pathogenic when exposed to IL-6. Co-culture with increasing doses of dexamethasone led to a synergistic increase in UCB Treg-induced apoptosis of conventional T cells (Tcons), which translated into significantly higher suppression of proliferating Tcons, especially at a lower Treg:Tcon ratio. Multiple injections of UCB Tregs led to their preferential accumulation in lung tissue in an immune injury xenogenic model. A significant decrease in lung resident cytotoxic CD8+ T cells (P = 0.0218) correlated with a sustained decrease in their systemic distribution compared with controls (P < 0.0001) (n = 7 per arm) as well as a decrease in circulating human soluble CD40 ligand level (P = 0.031). Tissue architecture was preserved in the treatment arm, and a significant decrease in CD3+ and CD8+ burden was evident in immunohistochemistry analysis. Conclusions: UCB Treg adoptive therapy is a promising therapeutic strategy for treatment of lung injury.

Original languageEnglish (US)
Pages (from-to)245-253
Number of pages9
JournalCytotherapy
Volume25
Issue number3
DOIs
StatePublished - Mar 2023
Externally publishedYes

Keywords

  • adoptive cell therapy
  • cord blood
  • lung inflammation
  • lung injury
  • regulatory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Transplantation
  • Cancer Research

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