Feline adipose-derived mesenchymal stem cells induce effector phenotype and enhance cytolytic function of CD8+ T cells
Abstract
Background: 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, particularly CD8+ T cells, remains to be elucidated.
Methods: Modified 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.
Results: Feline 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.
Conclusions: Our 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.
Keywords: CD8+ T cells; Feline mesenchymal stem cells; Granzyme B; Immunomodulation; Terminally differentiated effector cells.
Principal Scientist at Gallant
Dr. Nopmanee Taechangam, DVM, PhD, joined Gallant in 2021 and serves as a Principal Scientist specializing in veterinary regenerative medicine and stem cell therapy. A Fulbright scholar, she earned her PhD in Integrative Pathobiology from UC Davis, where her research focused on mesenchymal stem cell therapies for immune-mediated and infectious diseases in animals.
Dr. Taechangam has developed and validated multiple FDA-accepted potency assays for investigational veterinary cell therapies, supporting regulatory approval and product quality standards. Her work focuses on advancing safe, effective, off-the-shelf stem cell therapies for pets at scale.
