384:
Human Olfactory Mucosa-Derived Mesenchymal Stem Cells Suppress Cytotoxic Functions of CD8+ T-Lymphocytes and Natural Killer Cells
Sunday, March 4, 2018
South Hall A2 (Convention Center)
N Antonevich, Andrei Hancharou, O Buschik, A Rydna, V Chekan, E Strinkevich, Lawrence Dubuske
RATIONALE: Human olfactory mucosa-derived mesenchymal stem cells (hOM-MSCs) are promising for treatment of immune diseases. The immunomodulatory activities of hOM-MSCs are partially ascribed to CD4+ T and B-lymphocytes, macrophages, and dendritic cells. The effect of the hOM-MSCs on function of CD8 + cytotoxic lymphocytes (CTLs) and natural killer cells (NKCs) was assessed.

METHODS: hOM-MSC were generated from biopsies of patients (n=3) with non-inflammatory diseases of the nasal cavity. Peripheral blood mononuclear cells (PBMCs) (n=7) were cultured over hOM-MSCs in 10:1 ratio for 3 days. Expression of perforin, granzyme B and CD107a were analyzed in both CTLs and NKCs subsets. Jurkat cells were used as target cells. PBMCs and Jurkat were co-cultured in a 5:1 ratio for 2 h. Necrosis and apoptosis were detected by Annexin V (FITC) / To-PRO-3 staining.

RESULTS: The hOM-MSCs reduced granzyme B and perforin expression in NKCs, but not in CTLs. The hOM-MSCs suppressed both spontaneous and tumor cell-stimulated degranulation detected by CD107a expression in both CTLs and NKCs. The Viability assay showed that hOM-MSC-treated PBMCs possessed reduced ability to induce apoptosis in target cells (MSCs-treated group – 22.2 [range 18.2–27.3]%, control – 13.3 [range 12.0–15.4]%; р=0.02).

CONCLUSIONS: hOM-MSCs suppressed cytotoxic functions of CTLs and NKCs affecting expression of perforin, granzyme B, CD107a, which eventually led to the reduced ability to induce apoptosis in target tumor cells. The development of MSC-based cell therapy may be useful for diseases associated with excessive cytotoxicity.