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.

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“…36 Importantly, feline adMSCs also alter the phenotypical and functional characteristics of cytotoxic T cells (CD8+ T cells) and upregulate the expression of effector compounds such as granzyme B, interleukin-2 (IL-2) and the killer cell lectin-like receptor subfamily G1 (KLRG-1) in these cells. 37 Even more specifically, when MSCs are cocultured with T cells, they reduce CD8 and CD62L expression and upregulate CD57 and CD25. 37 Cumulatively, this phenotype switch means that cytotoxic T cells assume terminally differentiated, effector phenotypes and manifest an enhanced potency to fight off viral intruders.…”

“… 37 Even more specifically, when MSCs are co-cultured with T cells, they reduce CD8 and CD62L expression and upregulate CD57 and CD25. 37 Cumulatively, this phenotype switch means that cytotoxic T cells assume terminally differentiated, effector phenotypes and manifest an enhanced potency to fight off viral intruders. The latter interpretation of mechanistic studies indirectly agrees with the calicivirus etiology recently determined as a potential cause of FCGS.…”