Article
Culture-expanded human iNKT cells modulate regulatory and effector B cells of SSc patients
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Published: | October 8, 2019 |
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Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by a breach of immune tolerance towards endogenous antigens, leading to vasculopathy and progressive fibrosis of the skin and internal organs. The production of autoantibodies implicates a significant role of B cells in SSc pathogenesis. Invariant natural killer T (iNKT) cells are potent immunoregulatory T lymphocytes that are critical for maintaining immune tolerance by influencing other immune cells. Various studies suggest cognate interactions of iNKT cells with B cells shaping B-cell homeostasis. Our group has previously shown that SSc patients contain only very low iNKT-cell numbers in peripheral blood. Therefore, the purpose of this study was to examine the influence of culture-expanded human iNKT cells on B-cell phenotype and function of SSc patients.
Methods: iNKT cells from healthy donors were expanded ex vivo following a two-week protocol using rhIL-2 and α-GalCer. Such culture-expanded iNKT cells were further enriched by magnetic-activated cell sorting (MACS) to a purity >95%. B cells from healthy donors and SSc patients were also isolated using CD19 magnetic beads (purity >95%).
Results: To analyze effector and regulatory B cells in healthy volunteers and SSc patients, PBMCs were cultured in presence of LPS and CD40L. In SSc patients CD24+CD27+ regulatory B cells were significantly decreased compared to healthy controls. In addition, levels of IL-6 were increased while levels of IL-10 were decreased in SSc patients compared to healthy controls. This IL-6 bias could reflect the dysregulated immune homeostasis in SSc patients. We hypothesized that iNKT cells might restore a tolerogenic cytokine profile. Coculture of purified B cells from SSc patients with culture-expanded iNKT cells resulted in a significant decrease of IL-6 release measured by ELISA. Importantly, addition of iNKT cells did not change B-cell numbers.
Conclusion: In conclusion, culture-expanded iNKT cells are able to regulate B-cell homeostasis of SSc patients. Therefore, adoptive transfer of ex vivo expanded iNKT cells could restore immune tolerance in SSc patients with impaired iNKT-cell function.