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Int Immunopharmacol. 2019 Feb;67:427-440. doi: 10.1016/j.intimp.2018.12.040. Epub 2018 Dec 31.

Study of the adoptive immunotherapy on rheumatoid arthritis with Thymus-derived invariant natural killer T cells.

Author information

1
Medical School of Hebei University, Baoding, China.
2
People's Hospital of Nankai University, Tianjin, China. Electronic address: 940373961@qq.com.
3
Medical School of Hebei University, Baoding, China. Electronic address: mengming127@163.com.

Abstract

BACKGROUND:

The therapeutic effect of adoptive infusion of specific thymus-derived invariant natural killer T (iNKT) cells in a mouse model of rheumatoid arthritis (RA) was observed, and the mechanism of cellular immunotherapy was preliminarily explored.

METHODS:

Thymus-derived iNKT cells were infused to RA model mice, with α-GalCer as a positive control. Then, ankle swelling was examined, as well as inflammatory cell infiltration to the joint tissue (hematoxylin-eosin [H&E] staining). Flow cytometry (FCM) was used to assess iNKT cell and helper T lymphocyte (Th) subsets. Serum cytokine levels were determined with cytometric bead array (CBA), with protein expression levels of related transcription factors assessed by Western blot.

RESULTS:

The joint swelling in RA model animals were significantly improved in the cell therapy and α-GalCer positive control groups (P < 0.05). In addition, iNKT frequencies in peripheral blood, the thymus and spleen were increased significantly (P < 0.05). Meanwhile, iNKT1 subset frequencies in the thymus and spleen were decreased, as well as splenic Th1 and Th17 cell subset rates, and serum TNF-α, IFN-γ and IL-6 levels. The rates of iNKT2 and Th2 subsets as well as IL-4 and IL-10 levels were increased (P < 0.05). Thymus GATA-3 and splenic PLZF protein levels were increased (P < 0.05).

CONCLUSIONS:

Adoptive infusion of thymus-derived iNKT cells exerts therapeutic effects in RA mice by increasing iNKT frequency, altering the proportions of iNKT cell subsets, correcting Th cell subset imbalance and reducing the amounts of inflammatory cytokines.

KEYWORDS:

Cell adoptive therapy; Cytokines; Rheumatoid arthritis; Th1/Th2/Th17; Transcription factor; iNKT1/iNKT2

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