Abstract
BackgroundFeline adipose-derived mesenchymal stem cells (ASCs) engage with a variety of immune cells and have been used in several clinical trials for the treatment of inflammatory and immune-dysregulated diseases in cats, but the impact they exert on the functional characteristics on T cells, particularly CD8+ T cells, remains to be elucidated.MethodsModified mixed leukocyte reaction was performed between feline ASCs and PBMCs. Changes of cell cycle stages, phenotype and cellular senescence were determined through flow cytometry and gene expression analysis. Cytotoxicity assay was performed to evaluate CD8+ T cell effector function.ResultsFeline ASCs induce cell cycle arrest on CD8+ T cells in a contact-dependent manner, downregulate CD8 surface expression, and shift their phenotype toward terminally differentiated effector cells (CD57+, CD45R+, CD62L−). CD8 T cells interacted with feline ASCs also upregulated granzyme B, IL-2 and KLRG-1 expression and have enhanced cytotoxic potential, evident by the increased percentage of lysis on target cells.ConclusionsOur findings suggest that feline ASCs (1) alter CD8+ T cells toward terminally differentiated, proinflammatory effector phenotype with limited proliferative capacity, and (2) enhance their cytotoxic potential through granzyme B upregulation. These cytotoxic CD8+ T cells could aid in disease cure in cases caused by an underlying, unresolved viral infection.
Highlights
Feline adipose-derived mesenchymal stem cells (ASCs) engage with a variety of immune cells and have been used in several clinical trials for the treatment of inflammatory and immune-dysregulated diseases with varying degrees of success [1,2,3,4]
Feline ASCs induce cell cycle arrest in CD8+ T cells in a contact‐dependent manner We previously described that feline ASCs inhibit lymphocyte proliferation, both with or without cell–cell contact
We determined that the inhibition of lymphocyte proliferation by feline ASCs was due to cell cycle arrest in G0-G1 [3]
Summary
Feline adipose-derived mesenchymal stem cells (ASCs) engage with a variety of immune cells and have been used in several clinical trials for the treatment of inflammatory and immune-dysregulated diseases with varying degrees of success [1,2,3,4]. The cause is multifactorial, FCGS is characterized largely by a persistent inflammatory response from inappropriate T cell activation and tissue infiltration, predominantly with B cells and CD8+ T cells [6]. Feline adipose-derived mesenchymal stem cells (ASCs) engage with a variety of immune cells and have been used in several clinical trials for the treatment of inflammatory and immune-dysregulated diseases in cats, but the impact they exert on the functional characteristics on T cells, CD8+ T cells, remains to be elucidated
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